Trial Outcomes & Findings for Ramucirumab Plus Irinotecan for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma (NCT NCT03141034)

Last Updated: 2024-06-25

Results Overview

-PFS will be measured from date of study entry to first radiographic progression or death due to any cause. Radiographic progressive disease (PD) will be defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). For those who are alive and do not experience progression, the investigators will censor them at the time of loss to follow-up or at 30 months from the study entry, whichever comes first.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Up to 30 months from completion of treatment (up to 36 months)

Results posted on

2024-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Irinotecan Plus Ramucirumab -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Overall Study STARTED	40
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ramucirumab Plus Irinotecan for Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Age, Continuous	63 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	33 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	40 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 months from completion of treatment (up to 36 months)

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Progression-free Survival (PFS)	5.257 months Interval 2.957 to 6.341

SECONDARY outcome

Timeframe: Up to 30 months from completion of treatment (estimated to be 36 months)

-OS time will be measured from date of study entry to date of death from any cause. For those who are alive, the investigators will censor them at the time of loss to follow-up or at 30 months from the date of treatment discontinuation, whichever comes first.

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Overall Survival (OS)	8.51 months Interval 6.801 to 12.518

SECONDARY outcome

Timeframe: Up to 30 months from completion of treatment (estimated to be 36 months)

Population: 2 participants were not evaluable for this outcome measure.

-TTP is defined as the time from study entry until date of radiographic PD using RECIST v1.1 criteria. For those who are alive and do not experience progression, the investigators will censor them at the time of loss to follow-up or at 30 months from the study entry, whichever comes first. For those who are dead before progression, the investigators will consider death as the competing risk. If the number of death are very small, the investigators will censor them at time of death.

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=38 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Time to Progressive Disease (TTP)	5.454 months Interval 2.957 to 7.261

SECONDARY outcome

Timeframe: Up to end of treatment (estimated to be 6 months)

-BOR is defined as the best response across all time points from randomization until radiologically confirmed PD using RECIST, v1.1 criteria. Complete response defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions. Partial response defined as having a ≥30% decrease in sum of longest diameter (LD) of target lesions. Progressive disease defined as having a ≥20% increase in sum of LD of target lesions and ≥5 mm increase above nadir. Stable disease defined as small changes that did not meet above criteria.

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Best Overall Response (BOR) Complete response	1 Participants
Best Overall Response (BOR) Partial response	8 Participants
Best Overall Response (BOR) Stable disease	17 Participants
Best Overall Response (BOR) Progressive disease	6 Participants
Best Overall Response (BOR) Not evaluable	8 Participants

SECONDARY outcome

Timeframe: Up to end of treatment (estimated to be 6 months)

-ORR defined as confirmed complete response + confirmed partial response. Complete response defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions. Partial response defined as having a ≥30% decrease in sum of longest diameter (LD) of target lesions.

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Objective Response Rate (ORR)	9 Participants

SECONDARY outcome

Timeframe: Up to end of treatment (estimated to be 6 months)

-CBR defined as percentage of combined participants who have achieved confirmed complete response, confirmed partial response, and stable disease. Complete response defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions. Partial response defined as having a ≥30% decrease in sum of longest diameter (LD) of target lesions. Stable disease defined as small changes that did not meet above criteria nor the criteria for progressive disease.

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Clinical Benefit Rate (CBR)	26 Participants

SECONDARY outcome

Timeframe: Up to 30 days following completion of treatment (median length of follow-up 131.5 days, full range 15-687 days)

-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

Outcome measures

Outcome measures
Measure	Irinotecan Plus Ramucirumab n=40 Participants -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 non-cardiac chest pain	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 tardive dyskinesia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 anemia	29 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 anemia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 enlarged lymph node in groin	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 atrial fibrillation	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 palpitations	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 RBBB gallop splits	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 ear pain	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 vertigo	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 blurred vision	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 cataract	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 abdominal cramping	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 abdominal distension	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 abdominal pain	17 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 anal fissure	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 anal fistula	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 ascites	3 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 bloating	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 colitis	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 constipation	12 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 diarrhea	24 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 diarrhea	3 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dry mouth	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dyspepsia	6 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dysphagia	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 dysphagia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 early satiety	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 epigastric pain	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 5 esophageal hemorrhage	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 flatulence	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 gastroesophageal reflux disease	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 gum bleeding	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hemorrhoids	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypersalivation	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 mucositis oral	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 nausea	23 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 nausea	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 oral hemorrhage	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 oral pain	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 painful bowel movement	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 rectal hemorrhage	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 stomach pain	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 toothache	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 upper gastrointestinal hemorrhage	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 vomiting	16 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 vomiting	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 boil type lesion on left groin	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 chills	7 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 edema limbs	10 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 fatigue	24 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 fatigue	4 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 fever	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 flu-like symptoms	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 infusion related reaction	4 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 infusion related reaction	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 injection site reaction	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 night sweats	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 anaphylaxis	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 abdominal infection	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 bacteremia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 bronchial infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 G-tube infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 gum infection (bloody gums)	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hand sore infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 infection, source unknown	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 lung infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 lung infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 mucosal infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 nail infection (ingrown fingernail)	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 nail infection	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 upper respiratory infection	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 bruising	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 fall	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 alanine aminotransferase increased	9 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 alkaline phosphatase increased	13 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 alkaline phosphatase increased	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 aspartate aminotransferase increased	10 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 blood bilirubin increased	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 blood bilirubin increased	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 creatinine increased	4 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 lymphocyte count decreased	18 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 lymphocyte count decreased	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 lymphocyte count increased	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 neutrophil count decreased	7 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3-4 neutrophil count decreased	8 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 platelet count decreased	16 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 weight loss	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 weight loss	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 white blood cell decreased	17 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 white blood cell decreased	6 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 anorexia	17 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 anorexia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dehydration	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypercalcemia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hyperglycemia	8 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hyperkalemia	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypermagnesemia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypernatremia	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypoalbuminemia	22 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypocalcemia	9 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypoglycemia	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypokalemia	7 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 hypokalemia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hyponatremia	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 hyponatremia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypophosphatemia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 vitamin D deficiency	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 arthralgia	3 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 back pain	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 bone pain	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 exostosis	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 left groin pain	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 generalized muscle weakness	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 muscle weakness lower limb	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 myalgia	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 pain in extremity	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 cognitive disturbance	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 5 death due to disease progression	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 4 disease progression	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dizziness	11 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dysgeusia	4 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 headache	14 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 peripheral motor neuropathy	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 peripheral motor neuropathy	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 peripheral sensory neuropathy	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 seizure	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 stroke	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 anxiety	3 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 confusion	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 delirium	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 depression	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 insomnia	7 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 acute kidney injury	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dysuria	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 elevated white blood cell count in urine	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hematuria	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 hematuria	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 proteinuria	11 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 proteinuria	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 urinary incontinence	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 cough	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dyspnea	8 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 epistaxis	5 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hiccups	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 laryngeal inflammation	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 nasal congestion	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 postnasal drip	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 5 respiratory failure	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 runny nose	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 sinus disorder	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 sore throat	4 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 alopecia	16 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 dry skin	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 erythema	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hyperhidrosis	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 lesion on left leg	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 palmar plantar erythrodysesthesia syndrome	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 pruritus	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 rash acneiform	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 rash maculo-papular	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 rash on chest	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 razor burn	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 sweating	2 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 scalp pain	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 flushing	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hematoma	1 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypertension	7 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3-4 hypertension	7 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 hypotension	3 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 1-2 thromboembolic event	3 Participants
Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant Grade 3 thromboembolic event	4 Participants

Adverse Events

Irinotecan Plus Ramucirumab

Serious events: 23 serious events

Other events: 40 other events

Deaths: 37 deaths

Serious adverse events

Serious adverse events
Measure	Irinotecan Plus Ramucirumab n=40 participants at risk -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Cardiac disorders Atrial fibrillation	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Ascites	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Diarrhea	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Dysphagia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Esophageal hemorrhage	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Nausea	7.5% 3/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Upper gastrointestinal hemorrhage	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Vomiting	7.5% 3/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Fatigue	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Infusion related reaction	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Non-cardiac chest pain	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Bacteremia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Injury, poisoning and procedural complications Fall	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Alkaline phosphtase increased	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Blood bilirubin increased	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Weight loss	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Anorexia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hyponatremia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death due to disease progression	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Disease progression	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Cognitive disturbance	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Confusion	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Delirium	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Seizure	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Acute kidney injury	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Hematuria	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Dyspnea	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Hypertension	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Thromboembolic event	7.5% 3/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).

Other adverse events

Other adverse events
Measure	Irinotecan Plus Ramucirumab n=40 participants at risk -Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
Blood and lymphatic system disorders Anemia	75.0% 30/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Blood and lymphatic system disorders Enlarged lymph node groin	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Cardiac disorders Palpitations	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Cardiac disorders RBBB gallop splits	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Ear and labyrinth disorders Ear pain	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Ear and labyrinth disorders Vertigo	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Eye disorders Blurred vision	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Eye disorders Cataract	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Abdominal cramping	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Abdominal distension	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Abdominal pain	42.5% 17/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Anal fissure	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Anal fistula	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Ascites	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Bloating	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Colitis	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Constipation	30.0% 12/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Diarrhea	65.0% 26/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Dry mouth	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Dyspepsia	15.0% 6/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Dysphagia	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Early satiety	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Epigastric pain	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Flatulence	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Gastroesophageal reflux disease	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Gum bleeding	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Hemorrhoids	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Hypersalivation	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Mucositis oral	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Nausea	55.0% 22/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Oral hemorrhage	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Oral pain	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Painful bowel movement	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Rectal hemorrhage	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Stomach pain	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Toothache	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Gastrointestinal disorders Vomiting	37.5% 15/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Chills	17.5% 7/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Edema limbs	25.0% 10/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Fatigue	67.5% 27/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Fever	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Flu like symptoms	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Infusion related reaction	10.0% 4/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Injection site reaction	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Night sweats	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Non-cardiac chest pain	10.0% 4/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
General disorders Tardive dyskinesis	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Immune system disorders Anaphylaxis	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Abdominal infection	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Bronchial infection	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Finger nail infection (ingrown)	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations G-tube infection	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Gum infection (bloody)	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Hand sore infection	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Infection, source unknown	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Lung infection	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Muscosal infection	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Nail infection	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Upper respiratory infection	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Infections and infestations Urinary tract infection	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Injury, poisoning and procedural complications Bruising	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Alanine aminotransferase increased	22.5% 9/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Alkaline phosphatase increased	32.5% 13/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Aspartate aminotransferase increased	25.0% 10/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Blood bilirubin increased	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Creatinine increased	10.0% 4/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Lymphocyte count decreased	57.5% 23/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Lymphocyte count increased	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Neutrophil count decreased	37.5% 15/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Platelet count decreased	40.0% 16/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations Weight loss	15.0% 6/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Investigations White blood cell decreased	57.5% 23/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Anorexia	42.5% 17/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Dehydration	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypercalcemia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hyperglycemia	20.0% 8/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hyperkalemia	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypermagnesemia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypernatremia	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypoalbuminemia	55.0% 22/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypocalcemia	22.5% 9/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypoglycemia	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypokalemia	20.0% 8/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hyponatremia	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Hypophosphatemia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Metabolism and nutrition disorders Vitamin D deficiency	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 3/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Back pain	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Bone pain	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Exostosis	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Left groin pain	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Myalgia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Musculoskeletal and connective tissue disorders Pain in extremity	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Dizziness	27.5% 11/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Dysgeusia	10.0% 4/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Headache	35.0% 14/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Peripheral motor neuropathy	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Peripheral sensory neuropathy	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Seizure	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Nervous system disorders Stroke	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Psychiatric disorders Anxiety	7.5% 3/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Psychiatric disorders Depression	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Psychiatric disorders Insomnia	17.5% 7/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Dysuria	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Elevated WBC count in urine	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Hematuria	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Proteinuria	30.0% 12/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Renal and urinary disorders Urinary incontinence	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Cough	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Dyspnea	17.5% 7/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Epistaxis	12.5% 5/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Hiccups	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Laryngeal inflammation	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Postnasal drip	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Runny nose	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Sinus disorder	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Sore throat	10.0% 4/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Alopecia	40.0% 16/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Boil type lesion - left groin	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Dry skin	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Erythema	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Hyperhidrosis	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Lesion on left leg	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysesthesia	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Pruritus	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Rash acneiform	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Rash maculo-papular	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Rash on chest	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Razor burn	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Scalp pain	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Skin and subcutaneous tissue disorders Sweating	5.0% 2/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Flushing	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Hematoma	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Hypertension	32.5% 13/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Hypotension	7.5% 3/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Vascular disorders Thromboembolic event	10.0% 4/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.5% 1/40 • All-cause mortality was collected through completion of follow-up (up to a total of 36 months). Serious adverse events and adverse events were collected from start of treatment through 30 days following the last day of study treatment (median follow-up 131.5 days, full range 15-687 days).

Additional Information

Kian-Huat Lim, M.D., Ph.D.

Washington University School of Medicine

Phone: 314-362-6157

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place