Trial Outcomes & Findings for A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma (NCT NCT03445533)

Last Updated: 2022-11-08

Results Overview

The ORR for evaluable participants was calculated using the participant's best overall response (BOR). Per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) for target lesions as assessed by MRI, CT or X-ray: Complete Response (CR) - disappearance of all target lesions; Partial Response (PR) - \>=30% decrease from baseline of the sum of diameters of all target lesions; Stable Disease (SD) - does not qualify for CR, PR or Progression; Progressive Disease (PD) - 20% increase in the sum of diameters of target lesions. The calculation is derived from measuring the diameter (mm) of the target lesion at baseline and comparing target lesion diameter (mm) at intervals during treatment and/or post-treatment. Based on the percent of tumor decrease or increase, the appropriate category is assigned.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

481 participants

Primary outcome timeframe

Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).

Results posted on

2022-11-08

Participant Flow

The global Phase 3 study was conducted at academic cancer centers across 11 countries. Participating countries included United States, Australia, Canada, Czech Republic, France, Germany, Italy, Netherlands, Spain, Sweden, and United Kingdom.

The study was an open-label comparison of ipilimumab with and without intratumoral IMO-2125 (tilsotolimod) in participants with advanced melanoma who had disease progression while on or after PD-1 directed therapy. Study participants were randomized 1:1 to ipilimumab alone (Arm A) or ipilimumab with tilsotolimod given intratumorally (Arm B). Randomization was stratified on the duration of prior anti-PD-1 therapy, metastasis stage, and BRAF mutation status.

Participant milestones

Participant milestones
Measure	Arm A: Ipilimumab ipilimumab 3 mg/kg intravenous ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 (Tilsotolimod) Plus Ipilimumab IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod.
Overall Study STARTED	243	238
Overall Study COMPLETED	115	45
Overall Study NOT COMPLETED	128	193

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A: Ipilimumab ipilimumab 3 mg/kg intravenous ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 (Tilsotolimod) Plus Ipilimumab IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod.
Overall Study Progressive Disease	48	81
Overall Study Adverse Event	60	64
Overall Study Death	9	19
Overall Study Miscellaneous	0	16
Overall Study Withdrawal by Subject	3	4
Overall Study Physician Decision	1	3
Overall Study Sponsor Decision	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Never Received any Study Treatment	7	4

Baseline Characteristics

A Study of Tilsotolimod in Combo With Ipilimumab vs Ipilimumab Alone in Subjects With Anti-PD-1 Refractory Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A: Ipilimumab n=243 Participants ipilimumab 3 mg/kg intravenous Ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 Plus Ipilimumab n=238 Participants IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with Ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod	Total n=481 Participants Total of all reporting groups
Age, Continuous	64.3 years STANDARD_DEVIATION 13.73 • n=5 Participants	64.3 years STANDARD_DEVIATION 13.28 • n=7 Participants	64.3 years STANDARD_DEVIATION 13.49 • n=5 Participants
Sex: Female, Male Female	116 Participants n=5 Participants	105 Participants n=7 Participants	221 Participants n=5 Participants
Sex: Female, Male Male	127 Participants n=5 Participants	133 Participants n=7 Participants	260 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	211 Participants n=5 Participants	187 Participants n=7 Participants	398 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	45 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	207 Participants n=5 Participants	187 Participants n=7 Participants	394 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	44 Participants n=7 Participants	71 Participants n=5 Participants
Region of Enrollment Canada	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment Netherlands	9 Participants n=5 Participants	2 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Sweden	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Region of Enrollment Czechia	11 Participants n=5 Participants	19 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Italy	53 Participants n=5 Participants	40 Participants n=7 Participants	93 Participants n=5 Participants
Region of Enrollment United Kingdom	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Australia	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment France	71 Participants n=5 Participants	97 Participants n=7 Participants	168 Participants n=5 Participants
Region of Enrollment Germany	24 Participants n=5 Participants	14 Participants n=7 Participants	38 Participants n=5 Participants
Region of Enrollment Spain	29 Participants n=5 Participants	22 Participants n=7 Participants	51 Participants n=5 Participants
Baseline Melanoma Characteristics Primary Histology - Cutaneous	210 Participants n=5 Participants	203 Participants n=7 Participants	413 Participants n=5 Participants
Baseline Melanoma Characteristics Primary Histology - Mucosal	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Baseline Melanoma Characteristics Primary Histology - Other	18 Participants n=5 Participants	23 Participants n=7 Participants	41 Participants n=5 Participants
Baseline Melanoma Characteristics Primary Histology - Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Baseline Melanoma Staging IIIA	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Baseline Melanoma Staging IIIB	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Baseline Melanoma Staging IIIC	20 Participants n=5 Participants	35 Participants n=7 Participants	55 Participants n=5 Participants
Baseline Melanoma Staging IVM1A	36 Participants n=5 Participants	24 Participants n=7 Participants	60 Participants n=5 Participants
Baseline Melanoma Staging IVM1B	46 Participants n=5 Participants	24 Participants n=7 Participants	70 Participants n=5 Participants
Baseline Melanoma Staging IVM1C	137 Participants n=5 Participants	147 Participants n=7 Participants	284 Participants n=5 Participants
Baseline Melanoma Staging Other	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Baseline Elevated LDH (lactate dehydrogenase) Yes	124 Participants n=5 Participants	126 Participants n=7 Participants	250 Participants n=5 Participants
Baseline Elevated LDH (lactate dehydrogenase) No	112 Participants n=5 Participants	106 Participants n=7 Participants	218 Participants n=5 Participants
Baseline Elevated LDH (lactate dehydrogenase) Unknown	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
ECOG Performance Status 0	146 Participants n=5 Participants	150 Participants n=7 Participants	296 Participants n=5 Participants
ECOG Performance Status 1	96 Participants n=5 Participants	87 Participants n=7 Participants	183 Participants n=5 Participants
ECOG Performance Status 2	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
ECOG Performance Status 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
ECOG Performance Status 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Prior Systemic Anti-cancer Treatment PD-1 Inhibitor	242 Prior Treatments n=5 Participants	237 Prior Treatments n=7 Participants	479 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment BRAK Inhibitor	36 Prior Treatments n=5 Participants	35 Prior Treatments n=7 Participants	71 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment MEK Inhibitor	36 Prior Treatments n=5 Participants	33 Prior Treatments n=7 Participants	69 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Other	27 Prior Treatments n=5 Participants	38 Prior Treatments n=7 Participants	65 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Other Immunotherapy	14 Prior Treatments n=5 Participants	18 Prior Treatments n=7 Participants	32 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Cytokine	14 Prior Treatments n=5 Participants	10 Prior Treatments n=7 Participants	24 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Chemotherapy	8 Prior Treatments n=5 Participants	11 Prior Treatments n=7 Participants	19 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment CTLA-4 Inhibitor	5 Prior Treatments n=5 Participants	6 Prior Treatments n=7 Participants	11 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Oncolytic Virus	6 Prior Treatments n=5 Participants	5 Prior Treatments n=7 Participants	11 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Other Targeted Therapy	6 Prior Treatments n=5 Participants	5 Prior Treatments n=7 Participants	11 Prior Treatments n=5 Participants
Prior Systemic Anti-cancer Treatment Setting Unresectable/Metastatic Disease	214 Prior Treatment Settings n=5 Participants	200 Prior Treatment Settings n=7 Participants	414 Prior Treatment Settings n=5 Participants
Prior Systemic Anti-cancer Treatment Setting Adjuvant	58 Prior Treatment Settings n=5 Participants	76 Prior Treatment Settings n=7 Participants	134 Prior Treatment Settings n=5 Participants
Prior Systemic Anti-cancer Treatment Setting Neoadjuvant	6 Prior Treatment Settings n=5 Participants	2 Prior Treatment Settings n=7 Participants	8 Prior Treatment Settings n=5 Participants
Prior Systemic Anti-cancer Treatment Setting Other	1 Prior Treatment Settings n=5 Participants	4 Prior Treatment Settings n=7 Participants	5 Prior Treatment Settings n=5 Participants
Best Response from Last Prior Systemic Anti-cancer Treatment Complete Response	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Best Response from Last Prior Systemic Anti-cancer Treatment Partial Response	26 Participants n=5 Participants	23 Participants n=7 Participants	49 Participants n=5 Participants
Best Response from Last Prior Systemic Anti-cancer Treatment Stable Disease	49 Participants n=5 Participants	49 Participants n=7 Participants	98 Participants n=5 Participants
Best Response from Last Prior Systemic Anti-cancer Treatment Progressive Disease	135 Participants n=5 Participants	125 Participants n=7 Participants	260 Participants n=5 Participants
Best Response from Last Prior Systemic Anti-cancer Treatment Unknown	27 Participants n=5 Participants	38 Participants n=7 Participants	65 Participants n=5 Participants
Duration of Prior Anti-PD-1 Therapy Greater than or Equal to 12 Weeks	207 Participants n=5 Participants	204 Participants n=7 Participants	411 Participants n=5 Participants
Duration of Prior Anti-PD-1 Therapy Less than 12 Weeks	36 Participants n=5 Participants	34 Participants n=7 Participants	70 Participants n=5 Participants
BRAF Mutation Status and Prior Targeted Therapy BRAF Wild Type	188 Participants n=5 Participants	186 Participants n=7 Participants	374 Participants n=5 Participants
BRAF Mutation Status and Prior Targeted Therapy BRAF Mutation Positive with Prior Targeted Therapy	35 Participants n=5 Participants	34 Participants n=7 Participants	69 Participants n=5 Participants
BRAF Mutation Status and Prior Targeted Therapy BRAF Mutation Positive with no Prior Targeted Therapy	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: Response is measured from the date of randomization, until disease progression, death, or start of new anti-cancer therapy (up to 36 months).

Population: All percentages were based on the number of participants in the Intent-to-Treat (ITT) analysis set within each group. Participants with no disease assessment in the study were included in the Not Evaluable category under Best Overall Response.

Outcome measures

Outcome measures
Measure	Arm A: Ipilimumab n=243 Participants ipilimumab 3 mg/kg intravenous Ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 Plus Ipilimumab n=238 Participants IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with Ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod
Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 Complete Response	1 Participants	1 Participants
Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 Partial Response	20 Participants	20 Participants
Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 Stable Disease	45 Participants	61 Participants
Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 Progressive Disease	110 Participants	89 Participants
Summary of Independent Reviewer-Assessed Objective Response Rate (ORR) by RECIST v1.1 Not Evaluable	67 Participants	67 Participants

PRIMARY outcome

Timeframe: OS is measured from the date of randomization to the date of death from any cause (up to 36 months).

Population: All percentages were based on the number of participants in the Intent-to-Treat (ITT) analysis set within each group.

Efficacy measured by overall survival (OS) was defined as the number of participants alive compared to the number of participants that died by treatment group.

Outcome measures

Outcome measures
Measure	Arm A: Ipilimumab n=243 Participants ipilimumab 3 mg/kg intravenous Ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 Plus Ipilimumab n=238 Participants IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with Ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod
Summary of Overall Survival Died	166 Participants	165 Participants
Summary of Overall Survival Alive (Censored)	77 Participants	73 Participants

Adverse Events

Arm A: Ipilimumab

Serious events: 108 serious events

Other events: 218 other events

Deaths: 166 deaths

Arm B: IMO-2125 (Tilsotolimod) Plus Ipilimumab

Serious events: 119 serious events

Other events: 226 other events

Deaths: 165 deaths

Serious adverse events

Other adverse events

Additional Information

Head of Clinical Operations

Idera Pharmaceuticals, Inc.

Phone: 484-348-1605

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee There IS an agreement between the Principal Investigator and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Arm A: Ipilimumab n=243 participants at risk ipilimumab 3 mg/kg intravenous ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 (Tilsotolimod) Plus Ipilimumab n=238 participants at risk IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod.
Blood and lymphatic system disorders Anaemia	0.82% 2/243 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Blood and lymphatic system disorders Disseminated Intravascular Coagulation	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Blood and lymphatic system disorders Lymph Node Pain	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Blood and lymphatic system disorders Microcytic Anaemia	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Blood and lymphatic system disorders Neutropenia	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Cardiogenic Shock	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.84% 2/238 • Number of events 5 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Angina Pectoris	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Atrial Flutter	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Cardiac Arrest	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Cardiac Failure	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Cardiovascular Disorder	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Coronary Artery Occlusion	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Immune-mediated Myocarditis	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Myocarditis	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Cardiac disorders Pericardial Effusion	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Endocrine disorders Hypophysitis	2.5% 6/243 • Number of events 7 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	1.3% 3/238 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Endocrine disorders Adrenal Insufficiency	1.2% 3/243 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.84% 2/238 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Endocrine disorders Adrenocortical Insufficiency Acute	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Endocrine disorders Adrenocorticotropic Hormone Deficiency	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Endocrine disorders Lymphocytic Hypophysitis	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Eye disorders Retinal Detachment	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Colitis	5.3% 13/243 • Number of events 17 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	4.2% 10/238 • Number of events 10 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Immune-mediated Enterocolitis	4.5% 11/243 • Number of events 13 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	4.6% 11/238 • Number of events 14 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Diarrhoea	3.7% 9/243 • Number of events 9 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	1.3% 3/238 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Abdominal Pain	1.2% 3/243 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Nausea	1.2% 3/243 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Vomiting	1.2% 3/243 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Autoimmune Colitis	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.84% 2/238 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Gastritis	0.82% 2/243 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Gastrointestinal Toxicity	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Immune-mediated Pancreatitis	0.41% 1/243 • Number of events 3 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Intestinal Obstruction	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Pancreatitis	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.84% 2/238 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Small Intestinal Obstruction	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Subileus	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.84% 2/238 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Abdominal Pain Upper	0.41% 1/243 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Chronic Gastritis	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 2 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Gingival Bleeding	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.42% 1/238 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Large Intestinal Obstruction	0.41% 1/243 • Number of events 1 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	0.00% 0/238 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death

Other adverse events
Measure	Arm A: Ipilimumab n=243 participants at risk ipilimumab 3 mg/kg intravenous ipilimumab: Arm A: 4 doses administered intravenously at a dose of 3 mg/kg over 90 minutes on Weeks 1, 4, 7, and 10.	Arm B: IMO-2125 (Tilsotolimod) Plus Ipilimumab n=238 participants at risk IMO-2125 by intratumoral injection plus ipilimumab 3 mg/kg intravenous Tilsotolimod with ipilimumab: IMO-2125 intratumoral injection administered as 9 doses on Weeks 1, 2, 3, 5, 8, 11, 16, 20, and 24. WITH (Arm B): Ipilimumab administered as 4 doses on Weeks 2, 5, 8, and 11. in combination with tilsotolimod.
Blood and lymphatic system disorders Anaemia	12.8% 31/243 • Number of events 57 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	15.5% 37/238 • Number of events 61 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Diarrhoea	25.1% 61/243 • Number of events 85 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	29.4% 70/238 • Number of events 108 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Nausea	19.8% 48/243 • Number of events 56 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	22.7% 54/238 • Number of events 67 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Vomiting	12.3% 30/243 • Number of events 35 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	14.7% 35/238 • Number of events 40 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Constipation	9.5% 23/243 • Number of events 24 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	8.8% 21/238 • Number of events 23 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Abdominal Pain	5.3% 13/243 • Number of events 14 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	8.8% 21/238 • Number of events 24 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Dry Mouth	5.3% 13/243 • Number of events 13 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.5% 13/238 • Number of events 14 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Gastrointestinal disorders Abdominal Pain Upper	6.2% 15/243 • Number of events 17 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	3.4% 8/238 • Number of events 8 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
General disorders Asthenia	21.4% 52/243 • Number of events 60 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	33.2% 79/238 • Number of events 110 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
General disorders Pyrexia	11.5% 28/243 • Number of events 42 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	42.9% 102/238 • Number of events 211 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
General disorders Fatigue	14.4% 35/243 • Number of events 44 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	20.2% 48/238 • Number of events 75 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
General disorders Chills	2.9% 7/243 • Number of events 7 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	31.5% 75/238 • Number of events 120 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
General disorders Influenza Like Illness	2.1% 5/243 • Number of events 7 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	12.6% 30/238 • Number of events 61 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
General disorders Injection Site Pain	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	9.2% 22/238 • Number of events 30 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Hepatobiliary disorders Hepatocellular Injury	3.3% 8/243 • Number of events 11 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.9% 14/238 • Number of events 15 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Hepatobiliary disorders Cholestasis	2.1% 5/243 • Number of events 6 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.5% 13/238 • Number of events 14 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Investigations Aspartate Aminotransferase Increased	7.4% 18/243 • Number of events 25 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	13.4% 32/238 • Number of events 54 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Investigations Alanine Aminotransferase Increased	7.4% 18/243 • Number of events 27 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	13.0% 31/238 • Number of events 51 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Investigations Weight Decreased	4.9% 12/243 • Number of events 15 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	10.5% 25/238 • Number of events 33 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Investigations Blood Alkaline Phosphate Increased	3.3% 8/243 • Number of events 9 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	6.7% 16/238 • Number of events 19 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Investigations Gamma-glutamyltransferase Increased	1.2% 3/243 • Number of events 5 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	6.7% 16/238 • Number of events 23 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Metabolism and nutrition disorders Decreased Appetite	17.3% 42/243 • Number of events 46 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	18.9% 45/238 • Number of events 49 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Metabolism and nutrition disorders Hypokalaemia	5.8% 14/243 • Number of events 16 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	7.6% 18/238 • Number of events 26 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Metabolism and nutrition disorders Hyponatraemia	2.9% 7/243 • Number of events 8 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.9% 14/238 • Number of events 16 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Musculoskeletal and connective tissue disorders Arthralgia	7.4% 18/243 • Number of events 20 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	7.6% 18/238 • Number of events 24 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Musculoskeletal and connective tissue disorders Back Pain	7.0% 17/243 • Number of events 18 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.0% 12/238 • Number of events 12 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Musculoskeletal and connective tissue disorders Pain in Extremity	4.9% 12/243 • Number of events 13 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	4.6% 11/238 • Number of events 13 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Nervous system disorders Headache	6.2% 15/243 • Number of events 20 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	18.1% 43/238 • Number of events 60 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Psychiatric disorders Insomnia	5.8% 14/243 • Number of events 14 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	4.6% 11/238 • Number of events 11 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Respiratory, thoracic and mediastinal disorders Cough	5.8% 14/243 • Number of events 16 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	8.0% 19/238 • Number of events 19 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.5% 11/243 • Number of events 13 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	7.1% 17/238 • Number of events 20 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Skin and subcutaneous tissue disorders Pruritus	24.7% 60/243 • Number of events 70 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	23.9% 57/238 • Number of events 72 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Skin and subcutaneous tissue disorders Rash	9.1% 22/243 • Number of events 32 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	9.2% 22/238 • Number of events 30 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Skin and subcutaneous tissue disorders Vitiligo	1.2% 3/243 • Number of events 4 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	6.3% 15/238 • Number of events 17 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Skin and subcutaneous tissue disorders Erythema	2.1% 5/243 • Number of events 6 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.0% 12/238 • Number of events 14 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death
Vascular disorders Hypotension	0.00% 0/243 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death	5.0% 12/238 • Number of events 13 • Adverse events were collected from the signing of informed consent, through the duration of active study treatment (10 weeks active study for participants assigned to Arm A OR 24 weeks active study for participants assigned to Arm B) and then for 90 days after the last dose of study treatment. All-Cause Mortality was assessed for up to 36 months. Definitions aligned with FDA and ICH requirements. The grading of adverse events utilized the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03, which were defined as: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death