Trial Outcomes & Findings for A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy (NCT NCT03690388)

NCT ID: NCT03690388

Last Updated: 2025-09-25

Results Overview

Time to the earlier of either radiographic progressive disease (PD) or death from any cause.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

187 participants

Primary outcome timeframe

Up to approximately twenty months after the first subject is randomized. Time from randomization to the earlier of the following events: radiographic PD as determined by the blinded independent central review (BIRC) or death due to any cause.

Results posted on

2025-09-25

Participant Flow

Participant milestones

Participant milestones
Measure	Cabozantinib cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Overall Study STARTED	125	62
Overall Study COMPLETED	89	26
Overall Study NOT COMPLETED	36	36

Reasons for withdrawal

Reasons for withdrawal
Measure	Cabozantinib cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Overall Study Adverse Event	8	1
Overall Study Radiographic Progression	14	29
Overall Study Clinical deterioration	10	6
Overall Study Withdrawal by Subject	2	0
Overall Study Lack of Efficacy	1	0
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabozantinib n=125 Participants cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo n=62 Participants placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.	Total n=187 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
Age, Categorical Between 18 and 65 years	62 Participants n=99 Participants	29 Participants n=107 Participants	91 Participants n=206 Participants
Age, Categorical >=65 years	63 Participants n=99 Participants	33 Participants n=107 Participants	96 Participants n=206 Participants
Age, Continuous	65 years n=99 Participants	66 years n=107 Participants	66 years n=206 Participants
Sex: Female, Male Female	68 Participants n=99 Participants	34 Participants n=107 Participants	102 Participants n=206 Participants
Sex: Female, Male Male	57 Participants n=99 Participants	28 Participants n=107 Participants	85 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=99 Participants	6 Participants n=107 Participants	27 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	95 Participants n=99 Participants	53 Participants n=107 Participants	148 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=99 Participants	3 Participants n=107 Participants	12 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=99 Participants	0 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Asian	20 Participants n=99 Participants	14 Participants n=107 Participants	34 Participants n=206 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
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) White	90 Participants n=99 Participants	41 Participants n=107 Participants	131 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=99 Participants	5 Participants n=107 Participants	16 Participants n=206 Participants
Region of Enrollment Hong Kong	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment United States	10 participants n=99 Participants	9 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Czechia	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Thailand	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Region of Enrollment Russia	8 participants n=99 Participants	3 participants n=107 Participants	11 participants n=206 Participants
Region of Enrollment Austria	4 participants n=99 Participants	0 participants n=107 Participants	4 participants n=206 Participants
Region of Enrollment Netherlands	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Region of Enrollment South Korea	8 participants n=99 Participants	8 participants n=107 Participants	16 participants n=206 Participants
Region of Enrollment Brazil	11 participants n=99 Participants	4 participants n=107 Participants	15 participants n=206 Participants
Region of Enrollment Poland	9 participants n=99 Participants	4 participants n=107 Participants	13 participants n=206 Participants
Region of Enrollment France	8 participants n=99 Participants	3 participants n=107 Participants	11 participants n=206 Participants
Region of Enrollment Croatia	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Argentina	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Romania	3 participants n=99 Participants	1 participants n=107 Participants	4 participants n=206 Participants
Region of Enrollment Hungary	5 participants n=99 Participants	3 participants n=107 Participants	8 participants n=206 Participants
Region of Enrollment United Kingdom	4 participants n=99 Participants	3 participants n=107 Participants	7 participants n=206 Participants
Region of Enrollment Spain	10 participants n=99 Participants	9 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Canada	3 participants n=99 Participants	0 participants n=107 Participants	3 participants n=206 Participants
Region of Enrollment Belgium	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Region of Enrollment Taiwan	6 participants n=99 Participants	3 participants n=107 Participants	9 participants n=206 Participants
Region of Enrollment Italy	14 participants n=99 Participants	5 participants n=107 Participants	19 participants n=206 Participants
Region of Enrollment Mexico	3 participants n=99 Participants	0 participants n=107 Participants	3 participants n=206 Participants
Region of Enrollment Israel	3 participants n=99 Participants	0 participants n=107 Participants	3 participants n=206 Participants
Region of Enrollment Australia	5 participants n=99 Participants	1 participants n=107 Participants	6 participants n=206 Participants
Region of Enrollment Germany	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Receipt of prior lenvatinib	79 Participants n=99 Participants	39 Participants n=107 Participants	118 Participants n=206 Participants

PRIMARY outcome

Timeframe: Up to approximately twenty months after the first subject is randomized. Time from randomization to the earlier of the following events: radiographic PD as determined by the blinded independent central review (BIRC) or death due to any cause.

Population: All subjects randomized at the time of the analysis (N=187).

Time to the earlier of either radiographic progressive disease (PD) or death from any cause.

Outcome measures

Outcome measures
Measure	Cabozantinib n=125 Participants cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo n=62 Participants placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Progression Free Survival (PFS)	NA months Interval 5.7 to The CI 5.7 to 0.0 is not 0.0 but NA. The median PFS and upper bound of the CI could not be determined because not enough subjects on the cabozantinib arm had experienced progression at the time of the data cut-off to determine a median PFS. However, it was possible to estimate the HR at that timepoint based on the Cox Proportional Hazards Model.	1.9 months Interval 1.8 to 3.6

PRIMARY outcome

Timeframe: Six months after 100 subjects are randomized. Time from randomization to best overall response of confirmed complete response (CR) or confirmed partial response (PR) per BIRC per RECIST 1.1.

Population: The first 100 subjects randomized.

Proportion of subjects with the best overall response of complete response (CR) or partial response (PR).

Outcome measures

Outcome measures
Measure	Cabozantinib n=67 Participants cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo n=33 Participants placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Objective Response Rate (ORR)	15 percentage of participants Interval 5.8 to 29.3	0 percentage of participants Interval 0.0 to 14.8

Adverse Events

Cabozantinib

Serious events: 43 serious events

Other events: 112 other events

Deaths: 17 deaths

Placebo

Serious events: 18 serious events

Other events: 32 other events

Deaths: 14 deaths

Serious adverse events

Other adverse events

Additional Information

Exelixis Medical Information

Exelixis, Inc.

Phone: 855-292-3935

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreements with investigators vary; constant is our right to review results communications prior to public release, and embargo communications for a period of ≤ 60 days from submittal for review. We do not prohibit investigators from publishing, but we may require previously undisclosed confidential information, other than study results, to be removed from publications, and single-center publications are postponed until after publication of the trial's primary multicenter publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Cabozantinib n=125 participants at risk cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo n=62 participants at risk placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.2% 4/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	4.8% 3/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.2% 4/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.2% 4/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	6.5% 4/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Laryngeal necrosis	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.00% 0/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Diarrhoea	3.2% 4/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Abdominal distension	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Ascites	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Intestinal obstruction	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Large intestine perforation	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Oesophageal stenosis	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Vomiting	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Disease progression	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders General physical health deterioration	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Chest pain	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Fatigue	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Pain	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Oedema peripheral	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Arthralgia	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Back pain	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Bone lesion	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Pathological fracture	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Pneumonia	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Anal abscess	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations COVID-19	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Rectal abscess	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Bronchitis	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Influenza	0.00% 0/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Lower respiratory tract infection	0.00% 0/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Suspected COVID-19	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Metabolism and nutrition disorders Hypocalcaemia	1.6% 2/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Metabolism and nutrition disorders Decreased appetite	0.80% 1/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.

Other adverse events
Measure	Cabozantinib n=125 participants at risk cabozantinib (60 mg) once daily orally (qd) Cabozantinib: Tablets containing 60-mg or 20-mg cabozantinib once daily orally.	Placebo n=62 participants at risk placebo once daily orally (qd) Placebo: Tablets containing placebo equivalent of 60-mg or 20-mg cabozantinib once daily orally.
Skin and subcutaneous tissue disorders Alopecia	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Fatigue	32.8% 41/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	8.1% 5/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Asthenia	16.8% 21/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	14.5% 9/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
General disorders Mucosal inflammation	14.4% 18/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Metabolism and nutrition disorders Decreased appetite	26.4% 33/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	16.1% 10/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Metabolism and nutrition disorders Hypocalcaemia	24.0% 30/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Metabolism and nutrition disorders Hypomagnesaemia	14.4% 18/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	4.8% 3/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Metabolism and nutrition disorders Hypokalaemia	8.8% 11/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Alanine aminotransferase increased	25.6% 32/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Aspartate aminotransferase increased	25.6% 32/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Weight decreased	20.0% 25/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	4.8% 3/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Blood lactate dehydrogenase increased	9.6% 12/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Blood alkaline phosphatase increased	10.4% 13/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	3.2% 2/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Neutrophil count decreased	5.6% 7/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Investigations Platelet count decreased	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Vascular disorders Hypertension	29.6% 37/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	4.8% 3/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Diarrhoea	55.2% 69/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	3.2% 2/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Nausea	26.4% 33/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Vomiting	14.4% 18/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	8.1% 5/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Stomatitis	16.0% 20/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	3.2% 2/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Constipation	11.2% 14/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	8.1% 5/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Dry mouth	10.4% 13/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Abdominal pain	9.6% 12/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	3.2% 2/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Gastrointestinal disorders Dyspepsia	5.6% 7/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	47.2% 59/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Arthralgia	8.8% 11/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	6.5% 4/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Muscle spasms	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Pain in extremity	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	4.8% 3/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Musculoskeletal and connective tissue disorders Back pain	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	4.8% 3/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.0% 20/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	14.5% 9/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Nervous system disorders Dysgeusia	11.2% 14/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Respiratory, thoracic and mediastinal disorders Dysphonia	12.0% 15/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Nervous system disorders Headache	11.2% 14/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	1.6% 1/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Renal and urinary disorders Proteinuria	16.8% 21/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	3.2% 2/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Blood and lymphatic system disorders Thrombocytopenia	7.2% 9/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	0.00% 0/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Blood and lymphatic system disorders Anaemia	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	12.9% 8/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.
Infections and infestations Urinary tract infection	6.4% 8/125 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.	3.2% 2/62 • 1 year, 8 months. Safety assessments included evaluations of AEs, SAEs, deaths, clinical laboratory test results (hematology, serum chemistry, and urinalysis), physical examination findings, vital sign measurements, Eastern Cooperative Oncology Group performance status (ECOG PS), and 12-lead ECG recordings.