Trial Outcomes & Findings for IBI308 in Subjects With Advanced/Metastatic Solid Malignancies (NCT NCT03568539)

Last Updated: 2021-06-01

Results Overview

To evaluate preliminary anti-tumor activity (overall response rate, ORR) of IBI308 monotherapy in subjects with advanced/metastatic solid malignancies. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

39 participants

Primary outcome timeframe

29 months

Results posted on

2021-06-01

Participant Flow

Final analysis data cutoff date: Dec20. 39 subjects enrolled, 0 were ongoing.

3 subjects on Cohort 1 36 subjects on Cohort2

Participant milestones

Participant milestones
Measure	Cohort 1 Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Overall Study STARTED	3	36
Overall Study COMPLETED	3	36
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

IBI308 in Subjects With Advanced/Metastatic Solid Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=3 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=36 Participants Advanced/metastatic endometrial cancer. 200mg IV Q3W.	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=39 Participants	14 Participants n=41 Participants	15 Participants n=35 Participants
Age, Categorical >=65 years	2 Participants n=39 Participants	22 Participants n=41 Participants	24 Participants n=35 Participants
Age, Continuous	49.0 Years n=39 Participants	67.5 Years n=41 Participants	67.0 Years n=35 Participants
Sex: Female, Male Female	2 Participants n=39 Participants	36 Participants n=41 Participants	38 Participants n=35 Participants
Sex: Female, Male Male	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=39 Participants	4 Participants n=41 Participants	4 Participants n=35 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=39 Participants	31 Participants n=41 Participants	34 Participants n=35 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race (NIH/OMB) Asian	0 Participants n=39 Participants	3 Participants n=41 Participants	3 Participants n=35 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Black or African American	1 Participants n=39 Participants	4 Participants n=41 Participants	5 Participants n=35 Participants
Race (NIH/OMB) White	2 Participants n=39 Participants	28 Participants n=41 Participants	30 Participants n=35 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Region of Enrollment United States	3 participants n=39 Participants	36 participants n=41 Participants	39 participants n=35 Participants

PRIMARY outcome

Timeframe: 29 months

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=34 Participants Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Overall Response Rate (Confirmed)	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 2 years

To measure progression-free survival rate (PFS) Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non- target lesion, or the appearance of new lesions

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=34 Participants Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Progression-free Survival	17.14 Weeks Interval 11.9 to 50.3	10.86 Weeks Interval 5.7 to 12.0

SECONDARY outcome

Timeframe: 2 years

To measure duration of response (DOR)

Outcome measures

Outcome measures
Measure	Cohort 1 n=1 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=1 Participants Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Duration of Response	46.14 weeks Interval 46.14 to 46.14	15.29 weeks Interval 15.29 to 15.29

SECONDARY outcome

Timeframe: 2 years

Population: A total of 37 subjects (3 subjects in Cohort 1 and 34 subjects in Cohort 2) were analyzed for efficacy in the full analysis set (FAS) population as 2 subjects in Cohort 2 were excluded from the FAS because they had no postbaseline tumor assessment of efficacy.

To measure overall survival rate (OS)

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=34 Participants Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Overall Survival	NA Week Interval 50.3 to Median OS and OS range upper limit of 95% CI not reached	61.86 Week Interval 61.86 to OS range upper limit of 95% CI not reached

SECONDARY outcome

Timeframe: 2 years

Anti-Drug Antibodies will be tested to evaluate immunogenicity of IBI308

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=36 Participants Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Number of Participants With Detectable Anti- Drug Antibodies.	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 0-504h

To evaluate the Area Under the Curve \[AUC\] of IBI308.

Outcome measures

Outcome measures
Measure	Cohort 1 n=13 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Area Under the Curve (AUC [0-504h])	10400 hr*µg/mL Geometric Coefficient of Variation 34.4	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1: predose, 5 minutes, 1, 6, 24, 48, 168, and 336 hr post-end of infusion

To evaluate the Maximum Plasma Concentration \[Cmax\] of IBI308.

Outcome measures

Outcome measures
Measure	Cohort 1 n=13 Participants Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 Advanced/metastatic endometrial cancer. 200mg IV Q3W.
Maximum Plasma Concentration [Cmax]	55.8 µg/mL Geometric Coefficient of Variation 18.5	—

Adverse Events

Cohort 1

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Cohort 2

Serious events: 12 serious events

Other events: 34 other events

Deaths: 18 deaths

Serious adverse events

Other adverse events

Additional Information

YiBo

Innovent Biologics (Suzhou) Co., Ltd.

Phone: +8613382419112

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1 n=3 participants at risk Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=36 participants at risk Advanced/metastatic endometrial cancer 200mg IV Q3W.
Infections and infestations Urinary tract infection	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Infections and infestations Infection	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Infections and infestations Lung infection	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Hypoxia	66.7% 2/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Colitis	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Gastrointestinal fistula	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Nausea	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Endocrine disorders Hypothyroidism	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Vascular disorders Hypotension	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Cardiac disorders Cardiac failure	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Cardiac disorders Cardiac failure congestive	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
General disorders Pyrexia	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)

Measure	Cohort 1 n=3 participants at risk Advanced/metastatic cancers with TMB\>10 mutations per megabase (mut/Mb). 200mg IV Q3W.	Cohort 2 n=36 participants at risk Advanced/metastatic endometrial cancer 200mg IV Q3W.
Gastrointestinal disorders Nausea	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	22.2% 8/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Diarrhoea	100.0% 3/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	13.9% 5/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	16.7% 6/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Abdominal distension	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	11.1% 4/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Vomiting	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	13.9% 5/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Constipation	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Abdominal pain lower	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Colitis	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Gastrointestinal disorders Rectal haemorrhage	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
General disorders Fatigue	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	41.7% 15/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
General disorders Oedema peripheral	66.7% 2/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	16.7% 6/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
General disorders Pyrexia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
General disorders Chills	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
General disorders Non-cardiac chest pain	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Arthritis	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Metabolism and nutrition disorders Dehydration	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Metabolism and nutrition disorders Hypokalaemia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Metabolism and nutrition disorders Hyponatraemia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Pleural effusion	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Respiratory, thoracic and mediastinal disorders Pneumonitis	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Investigations Blood creatinine increased	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Investigations Weight decreased	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	11.1% 4/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Investigations Alanine aminotransferase increased	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Investigations Amylase increased	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Investigations Aspartate aminotransferase increased	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Investigations White blood cell count decreased	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Infections and infestations Urinary tract infection	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	16.7% 6/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Infections and infestations Upper respiratory tract infection	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Infections and infestations Lung infection	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Nervous system disorders Dizziness	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	8.3% 3/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Nervous system disorders Headache	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Nervous system disorders Hypoaesthesia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Vascular disorders Hypotension	66.7% 2/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Vascular disorders Hot flush	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Vascular disorders Deep vein thrombosis	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Skin and subcutaneous tissue disorders Rash erythematous	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Skin and subcutaneous tissue disorders Alopecia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Skin and subcutaneous tissue disorders Erythema	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	13.9% 5/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Endocrine disorders Hypothyroidism	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	11.1% 4/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Endocrine disorders Adrenal insufficiency	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Renal and urinary disorders Haematuria	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Renal and urinary disorders Hydronephrosis	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Injury, poisoning and procedural complications Fall	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	2.8% 1/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Injury, poisoning and procedural complications Skin laceration	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Cardiac disorders Cardiac failure	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Cardiac disorders Cardiac failure congestive	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Reproductive system and breast disorders Pelvic pain	0.00% 0/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	5.6% 2/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)
Psychiatric disorders Insomnia	33.3% 1/3 • 2 years Treatment-Emergent Adverse Events (TEAEs)	0.00% 0/36 • 2 years Treatment-Emergent Adverse Events (TEAEs)