Trial Outcomes & Findings for ARQ 197 in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancer (NCT NCT01075048)

Last Updated: 2021-04-08

Results Overview

Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause (as of data cutoff 12 Oct 2012).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

131 participants

Primary outcome timeframe

Baseline up to 80 weeks postdose

Results posted on

2021-04-08

Participant Flow

A total of 131 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 40 clinic sites (24 in the United States and 16 in Europe).

Of the 131, 9 participants enrolled into the Phase 1 cohort and 122 participants randomly assigned to ARQ 197 or placebo treatment in Phase 2. In Phase 2, 1 enrolled participant was not treated and therefore not included in the Safety Analysis Set.

Participant milestones

Participant milestones
Measure	Phase 1: ARQ 197+Cetuximab+Irinotecan Participants received an oral dose of ARQ197 capsules twice daily (BID) with a meal, in escalating doses of 120 milligram (mg), 240 mg, and 360 mg to 3 separate cohorts on Day 1 of Cycle 1 and Cycle 2. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed by 60 minutes with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: Placebo+Cetuximab+Irinotecan Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.
Overall Study STARTED	9	60	62
Overall Study Did Not Receive Treatment	0	1	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	9	60	62

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1: ARQ 197+Cetuximab+Irinotecan Participants received an oral dose of ARQ197 capsules twice daily (BID) with a meal, in escalating doses of 120 milligram (mg), 240 mg, and 360 mg to 3 separate cohorts on Day 1 of Cycle 1 and Cycle 2. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed by 60 minutes with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: Placebo+Cetuximab+Irinotecan Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.
Overall Study Death	4	17	12
Overall Study Start of other or new therapy	4	36	46
Overall Study Withdrawal by Subject	1	6	3
Overall Study Lost to Follow-up	0	1	1

Baseline Characteristics

ARQ 197 in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1: ARQ 197+Cetuximab+Irinotecan n=9 Participants Participants received an oral dose of ARQ197 capsules twice daily (BID) with a meal, in escalating doses of 120 milligram (mg), 240 mg, and 360 mg to 3 separate cohorts on Day 1 of Cycle 1 and Cycle 2. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed by 60 minutes with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: Placebo+Cetuximab+Irinotecan n=59 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=62 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Total n=130 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	40 Participants n=7 Participants	44 Participants n=5 Participants	90 Participants n=4 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	19 Participants n=7 Participants	18 Participants n=5 Participants	40 Participants n=4 Participants
Age, Continuous	55.2 years STANDARD_DEVIATION 14.69 • n=5 Participants	56.7 years STANDARD_DEVIATION 12.47 • n=7 Participants	57.4 years STANDARD_DEVIATION 12.57 • n=5 Participants	57.2 years STANDARD_DEVIATION 12.76 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	27 Participants n=7 Participants	36 Participants n=5 Participants	65 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	32 Participants n=7 Participants	26 Participants n=5 Participants	65 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	56 Participants n=7 Participants	59 Participants n=5 Participants	124 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to 80 weeks postdose

Population: PFS was assessed in the Full Analysis Set.

Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause (as of data cutoff 12 Oct 2012).

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=57 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=60 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 All participants who received ARQ 197 treatment.
Progression-Free Survival (PFS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy	7.3 months Interval 5.3 to 9.0	8.3 months Interval 5.6 to 10.8	—	—

PRIMARY outcome

Timeframe: Baseline up to 80 weeks postdose

Population: PFS was assessed in the Full Analysis Set.

Progression-free survival is defined as the time from randomization to the date of disease progression (PD) or death due to any cause (as of data cutoff 12 Oct 2012).

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=57 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=60 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 All participants who received ARQ 197 treatment.
Progression-Free Survival (PFS) Using Computed Best Response Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy	7.3 months Interval 5.3 to 9.0	8.3 months Interval 5.6 to 10.8	—	—

SECONDARY outcome

Timeframe: Baseline up to 2 years 10 months postdose

Population: Best overall response and objective response rate was assessed in the Safety Analysis Set.

Best overall tumor response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria included complete response (CR) defined as the disappearance of all target lesions; partial response (PR) defined as a ≥30% decrease in the longest diameter of target lesions; stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Objective response was defined as CR+PR.

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=57 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=60 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 All participants who received ARQ 197 treatment.
Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Complete response (CR)	0 Participants	0 Participants	—	—
Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Partial response (PR)	19 Participants	27 Participants	—	—
Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Stable disease (SD)	22 Participants	22 Participants	—	—
Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Progressive disease (PD)	13 Participants	9 Participants	—	—
Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Objective response (CR+PR)	19 Participants	27 Participants	—	—
Best Overall Tumor Response and Objective Response Rate Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Inevaluable	3 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: Baseline up to 5 years 1 month postdose

Population: Overall survival was assessed in the Full Analysis Set.

Overall survival is defined as the time from randomization date to the date of death.

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=57 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=60 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 All participants who received ARQ 197 treatment.
Overall Survival (OS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy Overall survival (29 Mar 2013 data cutoff)	16.9 months Interval 12.2 to 20.4	19.8 months Interval 13.4 to 27.0	—	—
Overall Survival (OS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy Overall survival (12 Oct 2012 data cutoff)	17.6 months Interval 11.3 to 20.4	NA months Interval 13.2 to Median OS was not reached.	—	—
Overall Survival (OS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy Overall survival (25 Jul 2013 data cutoff)	16.3 months Interval 11.6 to 20.4	19.8 months Interval 15.4 to 27.4	—	—
Overall Survival (OS) Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type K-ras Oncogene (KRAS) Who Have Received Front-Line Systemic Therapy Overall survival (20 Feb 2015 data cutoff)	16.3 months Interval 11.6 to 20.4	22.3 months Interval 15.4 to 27.0	—	—

SECONDARY outcome

Timeframe: Baseline up to 80 weeks postdose

Population: Duration of response and stable disease was assessed in the Full Analysis Set.

Duration of response was defined for participants with complete response (CR)/partial response (PR) as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease. Duration of stable disease (SD) was defined for participants whose best response was SD at the time from the randomization date to the date of the first documentation of progressive disease. Based on Response Evaluation Criteria in Solid Tumors version 1.1, CR is defined as a disappearance of all target lesions, PR is defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=57 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=60 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 All participants who received ARQ 197 treatment.
Duration of Response and Stable Disease Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type KRAS Who Have Received Front-Line Systemic Therapy Duration of response	29.42 weeks Standard Deviation 15.16	28.84 weeks Standard Deviation 16.03	—	—
Duration of Response and Stable Disease Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer With Wild-Type KRAS Who Have Received Front-Line Systemic Therapy Duration of stable disease	24.48 weeks Standard Deviation 11.48	29.76 weeks Standard Deviation 15.43	—	—

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose, up to 5 years 1 month

Population: Safety events were assessed in the Safety Analysis Set.

A treatment-emergent adverse event (TEAE) was defined as an AE that had an onset date on or after the first dose of study drug, cetuximab, or irinotecan up to and including 30 days after the last dose of any study drug and worsened in severity after the first dose of study drug relative to the pre-treatment state.

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=9 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=59 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=62 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 n=71 Participants All participants who received ARQ 197 treatment.
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Any TEAE	9 Participants	59 Participants	62 Participants	71 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Blood and Lymphatic System Disorders	4 Participants	28 Participants	23 Participants	27 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Anaemia	2 Participants	19 Participants	7 Participants	9 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Neutropenia	4 Participants	13 Participants	18 Participants	22 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Gastrointestinal Disorders	9 Participants	47 Participants	47 Participants	56 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Abdominal pain	3 Participants	16 Participants	12 Participants	15 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Constipation	1 Participants	11 Participants	10 Participants	11 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Diarrhea	5 Participants	30 Participants	33 Participants	38 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Nausea	6 Participants	27 Participants	28 Participants	34 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Stomatitis	1 Participants	4 Participants	7 Participants	8 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Vomiting	4 Participants	18 Participants	22 Participants	26 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy General Disorders & Administration Site Conditions	9 Participants	33 Participants	41 Participants	50 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Asthenia	0 Participants	6 Participants	8 Participants	8 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Fatigue	7 Participants	21 Participants	26 Participants	33 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Metabolism and Nutrition Disorders	3 Participants	20 Participants	23 Participants	26 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Decreased appetite	2 Participants	7 Participants	11 Participants	13 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Dehydration	1 Participants	6 Participants	7 Participants	8 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Hypomagnesaemia	2 Participants	6 Participants	6 Participants	8 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Nervous System Disorders	4 Participants	12 Participants	14 Participants	18 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Headache	2 Participants	4 Participants	7 Participants	9 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Psychiatric Disorders	5 Participants	10 Participants	12 Participants	17 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Insomnia	1 Participants	4 Participants	7 Participants	8 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Respiratory, Thoracic, and Mediastinal Disorders	5 Participants	20 Participants	17 Participants	22 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Cough	4 Participants	6 Participants	7 Participants	11 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Skin and Subcutaneous Tissue Disorders	9 Participants	49 Participants	58 Participants	67 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Alopecia	5 Participants	14 Participants	16 Participants	21 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Dermatitis acneiform	4 Participants	9 Participants	8 Participants	12 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Dry skin	4 Participants	10 Participants	11 Participants	15 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Rash	6 Participants	34 Participants	36 Participants	42 Participants
Treatment-Emergent Adverse Events Reported in ≥ 10% of Participants Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Subjects With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Skin fissures	3 Participants	3 Participants	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline up to 30 days after last dose, up to 5 years 1 month

Population: Safety events were assessed in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure	Phase 2: Placebo+Cetuximab+Irinotecan n=9 Participants Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=59 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=62 Participants Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	All ARQ 197 n=71 Participants All participants who received ARQ 197 treatment.
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Device-related infection	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Infections and Infestations	6 Participants	24 Participants	31 Participants	37 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Abscess jaw	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Abscess neck	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Bronchitis	0 Participants	1 Participants	3 Participants	3 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Candidiasis	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Cellulitis	1 Participants	1 Participants	2 Participants	3 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Cystitis	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Diverticulitis	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Ear infection	0 Participants	2 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Eye infection	0 Participants	0 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Folliculitis	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Fungal infection	1 Participants	1 Participants	1 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Gastroenteritis	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Herpes zoster	0 Participants	1 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Herpes simplex	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Hordeolum	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Infection	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Influenza	0 Participants	2 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Kidney infection	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Labyrinthitis	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Laryngitis	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Localised infection	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Nail infection	2 Participants	1 Participants	1 Participants	3 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Nasopharyngitis	0 Participants	1 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Oral pustule	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Paronychia	0 Participants	5 Participants	6 Participants	6 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Pharyngitis	1 Participants	0 Participants	0 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Pneumonia	1 Participants	1 Participants	1 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Pyoderma	0 Participants	2 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Rash pustular	0 Participants	1 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Respiratory tract infection	0 Participants	0 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Respiratory tract infection viral	0 Participants	1 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Sinusitis	0 Participants	0 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Skin infection	0 Participants	1 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Tooth abscess	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Tooth infection	0 Participants	2 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Tracheitis	0 Participants	1 Participants	0 Participants	0 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Tracheobronchitis	0 Participants	0 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Upper respiratory tract infection	0 Participants	0 Participants	3 Participants	3 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Urinary tract infection	0 Participants	4 Participants	2 Participants	2 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Urosepsis	0 Participants	0 Participants	1 Participants	1 Participants
Treatment-Emergent Infection and Infestation Adverse Events Following Treatment With Tivantinib (ARQ 197) in Combination With Irinotecan and Cetuximab in Participants With Metastatic Colorectal Cancer Who Have Received Front-Line Systemic Therapy Viral infection	0 Participants	0 Participants	1 Participants	1 Participants

Adverse Events

Phase 1: ARQ 197+Cetuximab+Irinotecan

Serious events: 3 serious events

Other events: 9 other events

Deaths: 6 deaths

Phase 2: Placebo+Cetuximab+Irinotecan

Serious events: 17 serious events

Other events: 59 other events

Deaths: 35 deaths

Phase 2: ARQ 197+Cetuximab+Irinotecan

Serious events: 13 serious events

Other events: 62 other events

Deaths: 35 deaths

Serious adverse events

Other adverse events

Additional Information

Contact for Clinical Trial Information

Daiichi Sankyo

Phone: 908-992-6400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Phase 1: ARQ 197+Cetuximab+Irinotecan n=9 participants at risk Participants received an oral dose of ARQ197 capsules twice daily (BID) with a meal, in escalating doses of 120 milligram (mg), 240 mg, and 360 mg to 3 separate cohorts on Day 1 of Cycle 1 and Cycle 2. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed by 60 minutes with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: Placebo+Cetuximab+Irinotecan n=59 participants at risk Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=62 participants at risk Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.
Blood and lymphatic system disorders Neutropenia	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Blood and lymphatic system disorders Anaemia	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Cardiac disorders Atrial fibrillation	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Abdominal pain	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Diarrhea	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Diverticulum intestinal	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Ileus	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Nausea	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Pneumoperitoneum	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Proctalgia	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Small intestinal obstruction	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.8% 4/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Small intestinal perforation	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Vomiting	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders General physical health deterioration	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Multi-organ failure	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Pneumatosis	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Pyrexia	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Immune system disorders Anaphylactic reaction	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Immune system disorders Hypersensitivity	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Diverticulitis	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Gastroenteritis	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Pneumonia	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Urinary tract infection	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Urosepsis	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Injury, poisoning and procedural complications Facial bones fracture	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Metabolism and nutrition disorders Dehydration	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Nervous system disorders Syncope	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Psychiatric disorders Anxiety	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Renal and urinary disorders Nephrolithiasis	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Renal and urinary disorders Renal failure acute	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.

Other adverse events
Measure	Phase 1: ARQ 197+Cetuximab+Irinotecan n=9 participants at risk Participants received an oral dose of ARQ197 capsules twice daily (BID) with a meal, in escalating doses of 120 milligram (mg), 240 mg, and 360 mg to 3 separate cohorts on Day 1 of Cycle 1 and Cycle 2. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed by 60 minutes with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: Placebo+Cetuximab+Irinotecan n=59 participants at risk Participants received placebo twice daily (BID) with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes, then over 60 minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.	Phase 2: ARQ 197+Cetuximab+Irinotecan n=62 participants at risk Participants received ARQ197 (recommended Phase 2 dose of 720 mg) daily with cetuximab and irinotecan until disease progression, unacceptable toxicity or other discontinuation. Cetuximab 500 mg/m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles followed 60 minutes later with irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Cetuximab and Irinotecan are administered on Day 1 and Day 15 of each 28 day cycle.
Blood and lymphatic system disorders Anaemia	22.2% 2/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	32.2% 19/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	11.3% 7/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Blood and lymphatic system disorders Leukopenia	22.2% 2/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	5.1% 3/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	8.1% 5/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Blood and lymphatic system disorders Neutropenia	44.4% 4/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	22.0% 13/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	29.0% 18/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	8.1% 5/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Cardiac disorders Left ventricular dysfunction	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Eye disorders Conjunctival irritation	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Eye disorders Ectropion	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Eye disorders Lacrimation increased	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Abdominal pain	33.3% 3/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	27.1% 16/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	19.4% 12/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Abdominal pain upper	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.8% 4/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	11.3% 7/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Cheilitis	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Constipation	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	18.6% 11/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	16.1% 10/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Diarrhoea	55.6% 5/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	50.8% 30/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	53.2% 33/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Dry mouth	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	5.1% 3/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	4.8% 3/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Flatulence	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	8.5% 5/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	8.1% 5/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Fatigue	77.8% 7/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	35.6% 21/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	41.9% 26/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Haemorrhoidal haemorrhage	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Lip dry	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Lip ulceration	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Nausea	66.7% 6/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	45.8% 27/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	45.2% 28/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Small intestinal obstruction	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.8% 4/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Stomatitis	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.8% 4/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	11.3% 7/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Gastrointestinal disorders Vomiting	44.4% 4/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	30.5% 18/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	35.5% 22/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Asthenia	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	10.2% 6/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	12.9% 8/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Chills	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	5.1% 3/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Hyperthermia	0.00% 0/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.5% 4/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Influenza-like illness	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Infusion site oedema	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Mucosal inflammation	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	5.1% 3/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	8.1% 5/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Non-cardiac chest pain	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Oedema peripheral	22.2% 2/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	8.5% 5/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.5% 4/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Pain	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.4% 2/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
General disorders Pyrexia	33.3% 3/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	11.9% 7/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	6.5% 4/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Candidiasis	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Cellulitis	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	3.2% 2/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Device-related infection	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Fungal infection	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.7% 1/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	1.6% 1/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.
Infections and infestations Kidney infection	11.1% 1/9 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/59 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.	0.00% 0/62 • Treatment-emergent adverse events (TEAE) were collected from baseline up to 30 days after last dose, up to 5 years 1 month. A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during treatment, having been absent at pre-treatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment relative to the pretreatment state, when the AE is continuous.