Trial Outcomes & Findings for Study to Evaluate Mechanisms of Acquired Resistance to Panitumumab (NCT NCT00891930)

NCT ID: NCT00891930

Last Updated: 2024-07-17

Results Overview

KRAS mutation status changed from wild-type at baseline to mutant at time of second biopsy in part 1, as measured by the PFS hazard ratio. Hazard ratio is presented as wild-type: mutant

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 74 participants
• Primary outcome timeframe: From baseline up to 152 weeks (from baseline to the time of the second biopsy prior to entering part 2) .
• Results posted on: 2024-07-17

Participant Flow

Upon radiographically confirmed disease progression per modified RECIST version 1.0, eligible subjects from part 1 proceeded to part 2 of the study to receive panitumumab plus ganitumab.

Participant milestones

Measure	Overall Study Period 1:Part 1 Panitumumab + Irinotecan Open label panitumumab 6 mg/kg every 2 weeks plus irinotecan 180 mg/m2 every 2 weeks Period 2:Part 2 Panitumumab + AMG479 Treatment with panitumumab 6 mg/kg every 2 weeks plus AMG 479 12 mg/kg every 2 weeks.
Part 1 Panitumumab + Irinotecan STARTED	74
Part 1 Panitumumab + Irinotecan COMPLETED	5
Part 1 Panitumumab + Irinotecan NOT COMPLETED	69
Part 2 Panitumumab + AMG479 STARTED	36
Part 2 Panitumumab + AMG479 COMPLETED	5
Part 2 Panitumumab + AMG479 NOT COMPLETED	31

Reasons for withdrawal

Measure	Overall Study Period 1:Part 1 Panitumumab + Irinotecan Open label panitumumab 6 mg/kg every 2 weeks plus irinotecan 180 mg/m2 every 2 weeks Period 2:Part 2 Panitumumab + AMG479 Treatment with panitumumab 6 mg/kg every 2 weeks plus AMG 479 12 mg/kg every 2 weeks.
Part 1 Panitumumab + Irinotecan Full Consent Withdrawn	2
Part 1 Panitumumab + Irinotecan Death	66
Part 1 Panitumumab + Irinotecan Lost to Follow-up	1
Part 2 Panitumumab + AMG479 Full Consent Withdrawn	1
Part 2 Panitumumab + AMG479 Death	30

Baseline Characteristics

Period 2 part 2 subjects are a subset of period 1 part 1 subjects

Baseline characteristics by cohort

Measure	Part 1 n=74 Participants Participants received panitumumab (6 mg/kg starting dose) with irinotecan (starting dose of 180 mg/m²) every 2 weeks (Q2W) during Part 1. Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.	Part 2 n=36 Participants Participants received panitumumab (6 mg/kg starting dose) with irinotecan (starting dose of 180 mg/m²) every 2 weeks (Q2W) during Part 1. Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.	Total n=110 Participants Total of all reporting groups
Age, Continuous Part 1	62.2 years STANDARD_DEVIATION 9.8 • n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	—	62.2 years STANDARD_DEVIATION 9.8 • n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Age, Continuous Part 2	—	62.9 years STANDARD_DEVIATION 10.1 • n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	62.9 years STANDARD_DEVIATION 10.1 • n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Sex: Female, Male Part 1 · Female	27 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	27 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Sex: Female, Male Part 1 · Male	47 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	47 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Sex: Female, Male Part 2 · Female	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	11 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	11 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Sex: Female, Male Part 2 · Male	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	25 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	25 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · American Indian or Alaska Native	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · Asian	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · Native Hawaiian or Other Pacific Islander	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · Black or African American	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · White	73 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	73 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · More than one race	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 1 · Unknown or Not Reported	1 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	1 Participants n=74 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · American Indian or Alaska Native	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · Asian	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · Native Hawaiian or Other Pacific Islander	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · Black or African American	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · White	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	35 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	35 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · More than one race	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	0 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Race (NIH/OMB) Part 2 · Unknown or Not Reported	0 Participants Period 2 part 2 subjects are a subset of period 1 part 1 subjects	1 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects	1 Participants n=36 Participants • Period 2 part 2 subjects are a subset of period 1 part 1 subjects
Subjects With Metastatic Colorectal Carcinoma Expressing Wild-type KRAS and Refractory to Oxaliplati Part 1	74 Participants n=74 Participants	0 Participants n=36 Participants	74 Participants n=110 Participants
Subjects With Metastatic Colorectal Carcinoma Expressing Wild-type KRAS and Refractory to Oxaliplati Part 2	0 Participants n=74 Participants	36 Participants n=36 Participants	36 Participants n=110 Participants

PRIMARY outcome

Timeframe: From baseline up to 152 weeks (from baseline to the time of the second biopsy prior to entering part 2) .

KRAS mutation status changed from wild-type at baseline to mutant at time of second biopsy in part 1, as measured by the PFS hazard ratio. Hazard ratio is presented as wild-type: mutant

Outcome measures

Measure	Part 1 n=74 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
PFS Hazard Ratio	0.365 months Interval 0.164 to 0.808

PRIMARY outcome

Timeframe: From time of randomization until confirmed complete response or partial response (part 2: up to 119 weeks)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Measure	Part 1 n=36 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Objective Response Rate in Part 2	0.00 percentage of participants Interval 0.0 to 9.74

SECONDARY outcome

Timeframe: from first dose of investigational product up to 152 weeks

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

Outcome measures

Measure	Part 1 n=74 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Objective Response Rate for Part 1	21.62 percentage of participants Interval 12.89 to 32.72

SECONDARY outcome

Timeframe: from first dose of investigational product up to 152 weeks

Time from the first dose of investigational product to the first date of disease progression per the modified RECIST v1.0 or death by any cause, initiating a new line of antitumor therapy, or receiving study treatment in Part 2, whichever is earlier in Part 1. Disease progression is a >= 20% increase in the sum of the longest diameter of the target lesions as compared to the smallest sum while on study per RECIST v1.0

Outcome measures

Measure	Part 1 n=74 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Progression-Free Survival for Part 1	4.6 months Interval 3.7 to 6.9

SECONDARY outcome

Timeframe: 119 weeks from the start of part 2, up to a maximum duration of 152 week

Time from the start of Part 2 to the first date of disease progression per the modified RECIST v1.0 or death by any cause, initiating a new line of antitumor therapy, or receiving study treatment in Part 2, whichever is earlier. Disease progression is a >= 20% increase in the sum of the longest diameter of the target lesions as compared to the smallest sum while on study per RECIST v1.0.

Outcome measures

Measure	Part 1 n=36 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Progression-Free Survival for Part 2	1.7 months Interval 1.6 to 1.8

SECONDARY outcome

Timeframe: from first dose of investigational product up to 152 weeks

Time from the first dose of investigational product to death from any cause in Part 1.

Outcome measures

Measure	Part 1 n=74 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Overall Survival for Part 1	11.6 months Interval 7.8 to 12.9

SECONDARY outcome

Timeframe: from the start of Part 2 up to 119 weeks

Time from the start of Part 2 to death from any cause.

Outcome measures

Measure	Part 1 n=36 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Overall Survival for Part 2	7.6 months Interval 5.6 to 12.3

SECONDARY outcome

Timeframe: from first dose of investigational product up to 152 weeks

Time from the first dose of investigational product to the date of first confirmed objective response in Part 1. An objective response is defined as a confirmed complete response or partial response per modified RECIST v1.0 criteria during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.

Outcome measures

Measure	Part 1 n=74 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Time to Response for Part 1	2.0 months Standard Deviation 0.4

SECONDARY outcome

Timeframe: from first dose of investigational product up to 152 weeks

Time from first confirmed objective response to disease progression per modified RECIST v1.0 in Part 1. An objective response is defined as a confirmed complete response or partial response per modified RECIST v1.0 criteria during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR; Disease progression is a >= 20% increase in the sum of the longest diameter of the target lesions as compared to the smallest sum while on study.

Outcome measures

Measure	Part 1 n=74 Participants Upon radiographically confirmed disease progression, participants proceeded to Part 2 of the study and received treatment with panitumumab (6 mg/kg starting dose) and ganitumab (12 mg/kg starting dose) Q2W.
Duration of Response for Part 1	7.7 months Interval 6.7 to 9.1

SECONDARY outcome

Timeframe: From time of randomization until confirmed complete response or partial response (part 2: up to 119 weeks)

Population: Due to no subjects having complete or partial responses, these Secondary Outcomes were not summarized.

Time to response was defined as the time from study day 1 to the first observation of an objective response (confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors [RECIST]). Duration of response was the time from the first observation of an objective response to the subsequent time of disease progression (per modified RECIST or clinical progression, whichever came first) or death due to any cause. Objective response = a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors [RECIST]. Per RECIST: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome data not reported

Adverse Events

Part 1 Panitumumab + Irinotecan

Serious events: 26 serious events

Other events: 74 other events

Deaths: 66 deaths

Part 2 Panitumumab + AMG479

Serious events: 8 serious events

Other events: 35 other events

Deaths: 30 deaths

Serious adverse events

Measure	Part 1 Panitumumab + Irinotecan n=74 participants at risk open label panitumumab 6 mg/kg every 2 weeks plus irinotecan 180 mg/m2 every 2 weeks	Part 2 Panitumumab + AMG479 n=36 participants at risk treatment with panitumumab 6 mg/kg every 2 weeks plus AMG 479 12 mg/kg every 2 weeks.
Blood and lymphatic system disorders Anaemia	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Blood and lymphatic system disorders Leukopenia	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Blood and lymphatic system disorders Neutropenia	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Cardiac disorders Cardiac failure	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Abdominal pain	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Diarrhoea	8.1% 6/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Ileus	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Intestinal obstruction	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Oesophagitis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Rectal haemorrhage	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	2.8% 1/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Stomatitis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Vomiting	4.1% 3/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Asthenia	4.1% 3/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Fatigue	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders General physical health deterioration	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Performance status decreased	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Hepatobiliary disorders Cholangitis	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	2.8% 1/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Hepatobiliary disorders Cholestasis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Immune system disorders Hypersensitivity	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	2.8% 1/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Infections and infestations Anal abscess	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Infections and infestations Bronchitis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Infections and infestations Device related infection	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Infections and infestations Gastroenteritis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Infections and infestations Staphylococcal sepsis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Infections and infestations Urinary tract infection	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Investigations Weight decreased	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Metabolism and nutrition disorders Decreased appetite	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Metabolism and nutrition disorders Hypokalaemia	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Metabolism and nutrition disorders Hypomagnesaemia	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Back pain	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Bone pain	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Muscle contracture	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Myalgia	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Paresis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Syncope	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Psychiatric disorders Confusional state	2.7% 2/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Renal and urinary disorders Renal failure acute	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Renal and urinary disorders Urinary retention	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Atelectasis	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 1/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Pyrexia	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	2.8% 1/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.

Other adverse events

Measure	Part 1 Panitumumab + Irinotecan n=74 participants at risk open label panitumumab 6 mg/kg every 2 weeks plus irinotecan 180 mg/m2 every 2 weeks	Part 2 Panitumumab + AMG479 n=36 participants at risk treatment with panitumumab 6 mg/kg every 2 weeks plus AMG 479 12 mg/kg every 2 weeks.
Gastrointestinal disorders Diarrhoea	74.3% 55/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	22.2% 8/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Asthenia	55.4% 41/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	33.3% 12/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Rash	52.7% 39/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	41.7% 15/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Nausea	51.4% 38/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	27.8% 10/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Metabolism and nutrition disorders Decreased Appetite	37.8% 28/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	13.9% 5/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Vomiting	37.8% 28/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	11.1% 4/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Mucosal Inflammation	33.8% 25/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	11.1% 4/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Dry Skin	32.4% 24/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	13.9% 5/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Alopecia	31.1% 23/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Metabolism and nutrition disorders Hypomagnesaemia	29.7% 22/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Constipation	27.0% 20/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	22.2% 8/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Skin Fissures	25.7% 19/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Abdominal Pain	24.3% 18/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	22.2% 8/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Psychiatric disorders Paronychia	24.3% 18/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	19.4% 7/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Skin Toxicity	18.9% 14/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Fatigue	17.6% 13/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	13.9% 5/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Pruritus	17.6% 13/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Blood and lymphatic system disorders Anaemia	16.2% 12/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Pyrexia	16.2% 12/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	13.9% 5/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Acne	13.5% 10/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders General Physical Health Deterioration	13.5% 10/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Back Pain	12.2% 9/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Eye disorders Conjunctivitis	12.2% 9/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Blood and lymphatic system disorders Neutropenia	12.2% 9/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Investigations Weight Decreased	12.2% 9/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Abdominal Pain Upper	10.8% 8/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	19.4% 7/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Cough	10.8% 8/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Dermatitis Acneiform	10.8% 8/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Psychiatric disorders Insomnia	10.8% 8/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.5% 7/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Metabolism and nutrition disorders Hypokalaemia	9.5% 7/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Xerosis	9.5% 7/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Dyspepsia	8.1% 6/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Folliculitis	8.1% 6/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Headache	8.1% 6/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	8.1% 6/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Renal and urinary disorders Urinary Tract Infection	8.1% 6/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Renal and urinary disorders Dysgeusia	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Erythema	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Oedema Peripheral	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	11.1% 4/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Paraesthesia	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Polyneuropathy	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Productive Cough	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Gastrointestinal disorders Stomatitis	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Trichomegaly	6.8% 5/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Abdominal Distension	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Chest Pain	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Eye disorders Dry Eye	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Renal and urinary disorders Dysuria	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Vascular disorders Haematoma	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Vascular disorders Haemorrhoids	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Nail Toxicity	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Neurotoxicity	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Cardiac disorders Tachycardia	5.4% 4/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	0.00% 0/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Hypomagnesaemia	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	13.9% 5/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Ear and labyrinth disorders Epistaxis	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Investigations Infusion Related Reaction	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Nail Bed Inflammation	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Nervous system disorders Palmar-Plantar Erythrodysaesthesia Syndrome	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	8.3% 3/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal Cancer	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Hepatic Pain	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Hypersensitivity	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.
General disorders Infection	0.00% 0/74 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.	5.6% 2/36 • Part 1: All-Cause Mortality was assessed up to 152 weeks and all other adverse events were collected up to 79 weeks; Part 2: All-Cause Mortality was assessed from start of part 2 up to 119 weeks from time of randomization and all other adverse events were collected up to 41 weeks from time of randomization.

Additional Information

Sandeep Bobby Reddy, Chief Medical Officer

ImmunityBio

Phone: 866-572-6436

Email: Bobby.Reddy@Immunitybio.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place