Trial Outcomes & Findings for Study of Tarloxotinib in Pts With NSCLC (EGFR Exon 20 Insertion, HER2-activating Mutations) & Other Solid Tumors With NRG1/ERBB Gene Fusions (NCT NCT03805841)

Last Updated: 2023-06-28

Results Overview

The primary objective of this study is to evaluate the objective response rate (ORR) of tarloxotinib according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for tumors assessed by CT or MRI: Complete Response (CR) - Disappearance of all target lesions and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm. Partial Response (PR) - ≥30% decrease in the sum of the longest diameter of the target lesions compared with baseline. The overall response rate in each cohort will be estimated as the number of subjects with a confirmed objective response (CR or PR) divided by the number of enrolled subjects in each respective cohort.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Through study completion, an average of 10 months.

Results posted on

2023-06-28

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A (N=11) Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring an EGFR exon 20 insertion. Subjects received taroxontinib 150 mg/m2 administered as a weekly 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.	Cohort B (N=22) Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring a HER2-activating mutation (including HER2 exon 20 insertions) who have not received prior HER2-directed therapy. Subjects received taroxontinib 150 mg/m2 administered as a weekly 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity	Cohort C (N=8) Previously treated advanced solid tumors harboring NRG1 or ERBB/HER-family gene fusions. Subjects received taroxontinib 150 mg/m2 administered as a weekly 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity
Overall Study STARTED	11	22	8
Overall Study COMPLETED	6	12	5
Overall Study NOT COMPLETED	5	10	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A (N=11) Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring an EGFR exon 20 insertion. Subjects received taroxontinib 150 mg/m2 administered as a weekly 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity.	Cohort B (N=22) Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring a HER2-activating mutation (including HER2 exon 20 insertions) who have not received prior HER2-directed therapy. Subjects received taroxontinib 150 mg/m2 administered as a weekly 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity	Cohort C (N=8) Previously treated advanced solid tumors harboring NRG1 or ERBB/HER-family gene fusions. Subjects received taroxontinib 150 mg/m2 administered as a weekly 1-hour IV infusion on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression or unacceptable toxicity
Overall Study Clinical Progression	2	0	0
Overall Study Death	0	3	1
Overall Study Lost to Follow-up	0	0	1
Overall Study Withdrawal by Subject	2	3	0
Overall Study Progressive disease according to RECIST 1.1 at any time during the study	1	4	1

Baseline Characteristics

Study of Tarloxotinib in Pts With NSCLC (EGFR Exon 20 Insertion, HER2-activating Mutations) & Other Solid Tumors With NRG1/ERBB Gene Fusions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A (N=11) n=11 Participants Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring an EGFR exon 20 insertion	Cohort B (N=22) n=22 Participants Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring a HER2-activating mutation (including HER2 exon 20 insertions) who have not received prior HER2-directed therapy	Cohort C (N=8) n=8 Participants Previously treated advanced solid tumors harboring NRG1 or ERBB/HER-family gene fusions	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=99 Participants	17 Participants n=107 Participants	6 Participants n=206 Participants	29 Participants n=7 Participants
Age, Categorical >=65 years	5 Participants n=99 Participants	5 Participants n=107 Participants	2 Participants n=206 Participants	12 Participants n=7 Participants
Sex: Female, Male Female	7 Participants n=99 Participants	11 Participants n=107 Participants	5 Participants n=206 Participants	23 Participants n=7 Participants
Sex: Female, Male Male	4 Participants n=99 Participants	11 Participants n=107 Participants	3 Participants n=206 Participants	18 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	4 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=99 Participants	19 Participants n=107 Participants	7 Participants n=206 Participants	36 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) Asian	3 Participants n=99 Participants	4 Participants n=107 Participants	3 Participants n=206 Participants	10 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	3 Participants n=7 Participants
Race (NIH/OMB) White	5 Participants n=99 Participants	13 Participants n=107 Participants	4 Participants n=206 Participants	22 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	5 Participants n=7 Participants
Smoking Status, n(%) Non-Smoker	9 Participants n=99 Participants	17 Participants n=107 Participants	5 Participants n=206 Participants	31 Participants n=7 Participants
Smoking Status, n(%) Former Smoker	2 Participants n=99 Participants	3 Participants n=107 Participants	2 Participants n=206 Participants	7 Participants n=7 Participants
Smoking Status, n(%) Current Smoker	0 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	3 Participants n=7 Participants

PRIMARY outcome

Timeframe: Through study completion, an average of 10 months.

Population: The Primary Analysis Set, referred to as the Safety Population in the protocol, is defined as all subjects who subjects who received at least 1 dose of tarloxotinib. The Primary Analysis Set will be the analysis population for the safety and efficacy analyses.

Outcome measures

Outcome measures
Measure	Cohort A (N=11) n=11 Participants Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring an EGFR exon 20 insertion	Cohort B (N=22) n=22 Participants Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring a HER2-activating mutation (including HER2 exon 20 insertions) who have not received prior HER2-directed therapy	Cohort C (N=8) n=8 Participants Previously treated advanced solid tumors harboring NRG1 or ERBB/HER-family gene fusions
ORR	0 percentage of participants Interval 0.0 to 28.49	13.6 percentage of participants Interval 2.91 to 34.91	0 percentage of participants Interval 0.0 to 36.94

Adverse Events

Cohort A (N=11)

Serious events: 4 serious events

Other events: 11 other events

Deaths: 5 deaths

Cohort B (N=22)

Serious events: 9 serious events

Other events: 22 other events

Deaths: 4 deaths

Cohort C (N=8)

Serious events: 3 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Rain Oncology Inc.

Phone: (510) 953-5559

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Cohort A (N=11) n=11 participants at risk Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring an EGFR exon 20 insertion	Cohort B (N=22) n=22 participants at risk Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring a HER2-activating mutation (including HER2 exon 20 insertions) who have not received prior HER2-directed therapy	Cohort C (N=8) n=8 participants at risk Previously treated advanced solid tumors harboring NRG1 or ERBB/HER-family gene fusions
Infections and infestations Lung infection	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Cardiac disorders Pericardial effusion	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Cardiac disorders Cardiac tamponade	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Metabolism and nutrition disorders Dehydration	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Dysphagia	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Vascular disorders Embolism	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Renal and urinary disorders Hydronephrosis	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Vascular disorders Hypertension	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
General disorders Pain	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Respiratory, thoracic and mediastinal disorders Pleuritic pain	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Respiratory, thoracic and mediastinal disorders Pulmonary hemmorrhage	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
General disorders Pyrexia	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Rash	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
General disorders Systemic inflammatory response syndrome	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).

Other adverse events
Measure	Cohort A (N=11) n=11 participants at risk Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring an EGFR exon 20 insertion	Cohort B (N=22) n=22 participants at risk Previously treated advanced/metastatic non-small cell lung cancer (NSCLC) who have a tumor harboring a HER2-activating mutation (including HER2 exon 20 insertions) who have not received prior HER2-directed therapy	Cohort C (N=8) n=8 participants at risk Previously treated advanced solid tumors harboring NRG1 or ERBB/HER-family gene fusions
Skin and subcutaneous tissue disorders Alopecia	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Eczema	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Pustular psoriasis	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Rosacea	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Rash	45.5% 5/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	40.9% 9/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	37.5% 3/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Dermatitis acneiform	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	31.8% 7/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	37.5% 3/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Dry skin	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	36.4% 8/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	25.0% 2/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Pruritus	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	27.3% 6/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	25.0% 2/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Rash maculo-papular	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	27.3% 6/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Erythema	18.2% 2/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Rash generalised	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Skin and subcutaneous tissue disorders Umbilical erythema	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Electrocardiogram QT prolonged	90.9% 10/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	86.4% 19/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	75.0% 6/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Alanine aminotransferase increased	18.2% 2/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	13.6% 3/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Aspartate aminotransferase increased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	18.2% 4/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Blood alkaline phosphatase increased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	13.6% 3/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Lymphocyte count decreased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Blood creatinine increased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Neutrophil count decreased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Lymphocyte count increased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations Weight decreased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Investigations White blood cell count decreased	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Diarrhoea	27.3% 3/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	18.2% 4/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	62.5% 5/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Nausea	27.3% 3/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	22.7% 5/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	25.0% 2/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Constipation	18.2% 2/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	13.6% 3/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Vomiting	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	13.6% 3/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	25.0% 2/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Paraesthesia oral	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	9.1% 2/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Abdominal discomfort	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Abdominal pain lower	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Abdominal distension	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Abdominal pain	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Ascites	9.1% 1/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Dry mouth	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Dyspepsia	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	4.5% 1/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Flatulence	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).
Gastrointestinal disorders Gastrointestinal pain	0.00% 0/11 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	0.00% 0/22 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).	12.5% 1/8 • From time of first dose, through 30 days after last dose, up to 12 months. Safety was assessed by repeated clinical evaluations including adverse events (AEs), suspected adverse reactions, unexpected events, serious AEs (SAEs), serious unexpected suspected adverse reactions, vital signs, physical examination, ECGs, clinical laboratory tests (serum chemistry, hematology, and urinalysis ).