Trial Outcomes & Findings for Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer (NCT NCT02713529)

NCT ID: NCT02713529

Last Updated: 2023-01-20

Results Overview

DLTs were evaluated by the Dose Level Review Team (DLRT). A DLT was defined as any grade \>=3 adverse event occurring during a DLT time window (21 day period from the initial administration of AMG 820 and pembrolizumab in combination), and if judged by the investigator to be related to the administration of AMG 820 and/or pembrolizumab.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 117 participants
• Primary outcome timeframe: The DLT evaluation period was Day 1 to Day 21
• Results posted on: 2023-01-20

Participant Flow

This study was conducted at 15 centers in Australia, Canada, United States of America, and Europe.

Part 1 was a phase Ib safety study comprised of two cohorts. Part 2 was a phase 2 safety and efficacy study comprised of 5 groups.

Participant milestones

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Overall Study STARTED	8	7	42	31	4	19	6
Overall Study COMPLETED	1	3	11	2	1	5	2
Overall Study NOT COMPLETED	7	4	31	29	3	14	4

Reasons for withdrawal

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Overall Study Withdrawal by Subject	3	1	4	2	0	1	1
Overall Study Lost to Follow-up	1	0	1	0	0	0	0
Overall Study Death	3	3	26	27	3	13	3

Baseline Characteristics

Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer

Baseline characteristics by cohort

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=8 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=7 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=42 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=31 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=4 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=19 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High n=6 Participants Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Total n=117 Participants Total of all reporting groups
Age, Customized 18-64 years	2 Participants n=5 Participants	6 Participants n=7 Participants	24 Participants n=5 Participants	18 Participants n=4 Participants	3 Participants n=21 Participants	7 Participants n=8 Participants	4 Participants n=8 Participants	64 Participants n=24 Participants
Age, Customized 65-74 years	6 Participants n=5 Participants	1 Participants n=7 Participants	15 Participants n=5 Participants	10 Participants n=4 Participants	1 Participants n=21 Participants	6 Participants n=8 Participants	2 Participants n=8 Participants	41 Participants n=24 Participants
Age, Customized 75-84 years	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	5 Participants n=8 Participants	0 Participants n=8 Participants	11 Participants n=24 Participants
Age, Customized >=85 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants	14 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	3 Participants n=8 Participants	43 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	26 Participants n=5 Participants	17 Participants n=4 Participants	3 Participants n=21 Participants	18 Participants n=8 Participants	3 Participants n=8 Participants	74 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	5 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	6 Participants n=7 Participants	36 Participants n=5 Participants	29 Participants n=4 Participants	4 Participants n=21 Participants	19 Participants n=8 Participants	6 Participants n=8 Participants	108 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	4 Participants n=24 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	5 Participants n=24 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	1 Participants n=8 Participants	4 Participants n=24 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	5 Participants n=7 Participants	39 Participants n=5 Participants	26 Participants n=4 Participants	4 Participants n=21 Participants	17 Participants n=8 Participants	5 Participants n=8 Participants	104 Participants n=24 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	4 Participants n=24 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0	6 Participants n=5 Participants	4 Participants n=7 Participants	19 Participants n=5 Participants	7 Participants n=4 Participants	1 Participants n=21 Participants	4 Participants n=8 Participants	2 Participants n=8 Participants	43 Participants n=24 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1	2 Participants n=5 Participants	3 Participants n=7 Participants	23 Participants n=5 Participants	24 Participants n=4 Participants	3 Participants n=21 Participants	15 Participants n=8 Participants	4 Participants n=8 Participants	74 Participants n=24 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Number of Prior Line of Therapy 0	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Number of Prior Line of Therapy 1	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	9 Participants n=24 Participants
Number of Prior Line of Therapy 2	1 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants	13 Participants n=4 Participants	1 Participants n=21 Participants	7 Participants n=8 Participants	3 Participants n=8 Participants	35 Participants n=24 Participants
Number of Prior Line of Therapy 3	4 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants	8 Participants n=4 Participants	0 Participants n=21 Participants	7 Participants n=8 Participants	3 Participants n=8 Participants	36 Participants n=24 Participants
Number of Prior Line of Therapy 4	1 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	5 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	18 Participants n=24 Participants
Number of Prior Line of Therapy 5	2 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=8 Participants	0 Participants n=8 Participants	19 Participants n=24 Participants
Number of Prior Line of Therapy >5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Disease Stage at Screening Stage I	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	2 Participants n=24 Participants
Disease Stage at Screening Stage II	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	9 Participants n=24 Participants
Disease Stage at Screening Stage III	0 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=8 Participants	1 Participants n=8 Participants	9 Participants n=24 Participants
Disease Stage at Screening Stage IV	6 Participants n=5 Participants	6 Participants n=7 Participants	35 Participants n=5 Participants	26 Participants n=4 Participants	3 Participants n=21 Participants	16 Participants n=8 Participants	5 Participants n=8 Participants	97 Participants n=24 Participants

PRIMARY outcome

Timeframe: The DLT evaluation period was Day 1 to Day 21

Population: Safety Analysis Set

DLTs were evaluated by the Dose Level Review Team (DLRT). A DLT was defined as any grade >=3 adverse event occurring during a DLT time window (21 day period from the initial administration of AMG 820 and pembrolizumab in combination), and if judged by the investigator to be related to the administration of AMG 820 and/or pembrolizumab.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=8 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=7 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=41 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=31 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=4 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=19 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High n=6 Participants Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Participants With Dose Limiting Toxicities (DLT) Participants with treatment emergent DLTs	0 Participants	1 Participants	3 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Autoimmune pancreatitis	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Autoimmune hepatitis	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Cholecystitis	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Electrolyte imbalance	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Fatigue	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Aspartate aminotransferase increased	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Lipase increased	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Epilepsy	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Rash generalised	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Participants With Dose Limiting Toxicities (DLT) DLT: Rash maculo-papular	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2

Population: Safety Analysis Set

TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=8 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=7 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=41 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=31 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=4 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=19 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High n=6 Participants Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Participants With Treatment -Emergent Adverse Events (TEAEs) >=1 TEAE	8 Participants	7 Participants	41 Participants	31 Participants	4 Participants	19 Participants	6 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Grade >=3	7 Participants	7 Participants	40 Participants	30 Participants	4 Participants	19 Participants	6 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Grade >=4	2 Participants	4 Participants	24 Participants	26 Participants	2 Participants	12 Participants	4 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Grade >=5	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning
Participants With Treatment -Emergent Adverse Events (TEAEs) Serious AE	5 Participants	2 Participants	31 Participants	23 Participants	3 Participants	11 Participants	5 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Leading to interruption of AMG 820	4 Participants	3 Participants	23 Participants	7 Participants	1 Participants	7 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Leading to discontinuation AMG 820	0 Participants	0 Participants	6 Participants	5 Participants	2 Participants	1 Participants	3 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) ---- SAE leading to d/c AMG 820	0 Participants	0 Participants	4 Participants	4 Participants	1 Participants	0 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) ----Non-serious AE leading to d/c AMG 820	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Leading to discontinuation of PEM	1 Participants	0 Participants	7 Participants	5 Participants	2 Participants	1 Participants	3 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) ---- SAE leading to d/c PEM	0 Participants	0 Participants	4 Participants	4 Participants	1 Participants	0 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) ----Non-serious AE leading to d/c PEM	1 Participants	0 Participants	3 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Fatal TEAE	1 Participants	0 Participants	4 Participants	3 Participants	0 Participants	3 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) TEAE related to study procedure/activity	0 Participants	1 Participants	11 Participants	5 Participants	0 Participants	3 Participants	1 Participants

PRIMARY outcome

Timeframe: Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2

Population: Safety Analysis Set

TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=8 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=7 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=41 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=31 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=4 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=19 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High n=6 Participants Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment >=1 TEAE	5 Participants	7 Participants	41 Participants	25 Participants	4 Participants	14 Participants	6 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Grade >=3	3 Participants	5 Participants	28 Participants	11 Participants	1 Participants	10 Participants	6 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Grade >=4	1 Participants	1 Participants	5 Participants	5 Participants	0 Participants	2 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Grade >=5	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Serious AE	2 Participants	2 Participants	12 Participants	4 Participants	0 Participants	3 Participants	3 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Leading to interruption of AMG 820	2 Participants	3 Participants	16 Participants	7 Participants	0 Participants	5 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Leading to discontinuation AMG 820	0 Participants	0 Participants	3 Participants	3 Participants	1 Participants	0 Participants	3 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment ---- SAE leading to d/c AMG 820	0 Participants	0 Participants	3 Participants	2 Participants	0 Participants	0 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment ----Non-serious AE leading to d/c AMG 820	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Leading to discontinuation of PEM	0 Participants	0 Participants	4 Participants	3 Participants	1 Participants	0 Participants	3 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment ---- SAE leading to d/c PEM	0 Participants	0 Participants	3 Participants	2 Participants	0 Participants	0 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment ----Non-serious AE leading to d/c PEM	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Fatal TEAE	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment TEAE related to study procedure/activity	0 Participants	0 Participants	8 Participants	2 Participants	0 Participants	3 Participants	1 Participants

PRIMARY outcome

Timeframe: Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2

Population: Safety Analysis Set

TEAEs include any adverse event starting on or after the first dose of AMG 820 or pembrolizumab. Relation to study drugs was determined by the investigator. Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. Errors in the case report form design resulted in investigators misunderstanding the CTCAE definition for severity grade 5. Therefore data are not reported for severity grade 5. Readers are referred to the 'Fatal TEAE' line in the table below for counts of participants who died during the TEAE timeframe.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=8 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=7 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=41 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=31 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=4 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=19 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High n=6 Participants Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment ---- SAE leading to d/c PEM	0 Participants	0 Participants	3 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment ----Non-serious AE leading to d/c PEM	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Fatal TEAE	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment TEAE related to study procedure/activity	0 Participants	0 Participants	9 Participants	3 Participants	0 Participants	2 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment >=1 TEAE	5 Participants	7 Participants	39 Participants	24 Participants	4 Participants	13 Participants	6 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Grade >=3	2 Participants	5 Participants	29 Participants	9 Participants	1 Participants	10 Participants	4 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Grade >=4	1 Participants	1 Participants	5 Participants	4 Participants	0 Participants	2 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Grade >=5	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning	NA Participants investigator misunderstanding of meaning
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Serious AE	2 Participants	2 Participants	16 Participants	5 Participants	0 Participants	3 Participants	4 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Leading to interruption of PEM	1 Participants	3 Participants	15 Participants	6 Participants	0 Participants	5 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Leading to discontinuation AMG 820	0 Participants	0 Participants	4 Participants	2 Participants	1 Participants	1 Participants	3 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment ---- SAE leading to d/c AMG 820	0 Participants	0 Participants	3 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment ----Non-serious AE leading to d/c AMG 820	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants	1 Participants
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Leading to discontinuation of PEM	0 Participants	0 Participants	5 Participants	2 Participants	1 Participants	1 Participants	3 Participants

PRIMARY outcome

Timeframe: Baseline: Day -28; Treatment: up to Month 13.7

Population: Safety Analysis Set

ORR was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). During treatment radiographic imaging was performed at Week 10 and repeated at least every 10 weeks until disease progression.

Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=15 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=41 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=31 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=4 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=19 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=6 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST)	0.0 percentage of participants Interval 0.0 to 0.0	4.9 percentage of participants Interval 0.6 to 16.53	0.0 percentage of participants Interval 0.0 to 0.0	0.0 percentage of participants Interval 0.0 to 0.0	5.3 percentage of participants Interval 0.13 to 26.03	0.0 percentage of participants Interval 0.0 to 0.0	—

SECONDARY outcome

Timeframe: Day 1 up to Month 16 (max time to censoring)

Population: Safety Analysis Set

Time to response was defined as the time from first dose of AMG 820 until first documented complete or partial response per irRECIST divided by 365.25 days/12.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=2 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=1 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded	—	2.1587 month Interval 2.004 to 2.168	—	—	2.0698 month with a single participant contributing data, the full range values equal the observed value.	—	—

SECONDARY outcome

Timeframe: Day 1 up to 14.4 months (max time to censoring)

Population: Safety Analysis Set

Time to progression was defined as the time from first dose of AMG 820 until first documented progressive disease per irRECIST divided by 365.25 days/12.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=10 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=29 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=13 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=3 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=8 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=4 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Time to Progression (TTP) for Participants Who Had Progressive Disease	2.1865 month Interval 0.46 to 5.552	3.0691 month Interval 0.559 to 8.411	2.3878 month Interval 0.296 to 4.698	4.6762 month Interval 2.07 to 6.604	6.0863 month Interval 1.15 to 11.992	7.7864 month Interval 1.938 to 13.667	—

SECONDARY outcome

Timeframe: Day 1 up to Month 6 or Month 12

Population: Safety Analysis Set

Overall survival time was calculated as the number of days from the first administration of AMG 820 to date of death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive at Month 6 and Month 12.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=15 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=41 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=31 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=4 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=19 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=6 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 Month 6	59.077 percentage of participants Interval 32.25 to 78.28	53.915 percentage of participants Interval 40.0 to 63.93	16.705 percentage of participants Interval 7.4 to 29.24	75.000 percentage of participants Interval 22.34 to 94.63	52.105 percentage of participants Interval 31.91 to 68.93	41.667 percentage of participants Interval 9.26 to 72.47	—
Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 Month 12	47.262 percentage of participants Interval 21.19 to 69.63	38.963 percentage of participants Interval 25.77 to 51.94	8.353 percentage of participants Interval 2.22 to 19.81	25.00 percentage of participants Interval 2.08 to 60.89	34.737 percentage of participants Interval 17.37 to 52.79	41.667 percentage of participants Interval 9.26 to 72.47	—

SECONDARY outcome

Timeframe: Day 1 up to Month 6 or Month 12

Population: Safety Analysis Set

Progression-free survival time was calculated as the number of days from the first administration of AMG 820 to date of progressive disease or death or censoring divided by (365.25/12). Data are reported as the percentage of participants who were alive and progression-free at Month 6 and Month 12.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=15 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=41 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient n=31 Participants Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer n=4 Participants Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve n=19 Participants Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low n=6 Participants Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12 Month 6	10.476 percentage of participants Interval 1.23 to 31.4	13.490 percentage of participants Interval 5.99 to 24.04	0.000 percentage of participants Interval 0.0 to 0.0	25.000 percentage of participants Interval 2.08 to 60.89	26.471 percentage of participants Interval 10.67 to 45.41	33.333 percentage of participants Interval 7.37 to 62.95	—
Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12 Month 12	0.000 percentage of participants Interval 0.0 to 0.0	5.396 percentage of participants Interval 1.36 to 13.77	0.000 percentage of participants Interval 0.0 to 0.0	0.000 percentage of participants Interval 0.0 to 0.0	6.618 percentage of participants Interval 0.77 to 21.97	33.333 percentage of participants Interval 7.37 to 62.95	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2 Cycle 1	2.0 hour Interval 1.0 to 170.0	2.0 hour Interval 1.0 to 7.0	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2 Cycle 2	3.00 hour Interval 1.0 to 25.0	2.00 hour Interval 1.0 to 25.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2 Cycle 1	331 ug/mL Geometric Coefficient of Variation 27	485 ug/mL Geometric Coefficient of Variation 23	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2 Cycle 2	363 ug/mL Geometric Coefficient of Variation 32	536 ug/mL Geometric Coefficient of Variation 21	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

AUClast is the area under the serum concentration-time curve from time zero to time of last quantifiable concentration.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 Cycle 1	55100 hr*ug/mL Geometric Coefficient of Variation 37	80400 hr*ug/mL Geometric Coefficient of Variation 33	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 Cycle 2	55200 hr*ug/mL Geometric Coefficient of Variation 38	73500 hr*ug/mL Geometric Coefficient of Variation 45	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

AUCtau is the area under the serum concentration-time curve over the dose interval tau, with tau equal to 21 days.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 Cycle 1	59300 hr*ug/mL Geometric Coefficient of Variation 33	90000 hr*ug/mL Geometric Coefficient of Variation 29	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 Cycle 2	75400 hr*ug/mL Geometric Coefficient of Variation 35	114000 hr*ug/mL Geometric Coefficient of Variation 31	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2 Cycle 1	49.9 ug/mL Geometric Coefficient of Variation 51	90.9 ug/mL Geometric Coefficient of Variation 35	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2 Cycle 2	78.7 ug/mL Geometric Coefficient of Variation 66	199 ug/mL Geometric Coefficient of Variation 34	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2 Cycle 1	217 hour Geometric Coefficient of Variation 26	214 hour Geometric Coefficient of Variation 24	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2 Cycle 2	170 hour Geometric Coefficient of Variation 16	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Volume of distribution observed at terminal phase after intravenous dosing.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 Cycle 1	5200 liter Geometric Coefficient of Variation 35	4110 liter Geometric Coefficient of Variation 25	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 Cycle 2	4560 liter Geometric Coefficient of Variation 21	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Drug clearance observed after intravenous dosing.

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 Cycle 1	16.6 liter/hour Geometric Coefficient of Variation 37	13.3 liter/hour Geometric Coefficient of Variation 33	—	—	—	—	—
AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 Cycle 2	18.6 liter/hour Geometric Coefficient of Variation 30	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36

Population: Pharmacovigilence Analysis Set contains all participants who received at least 1 dose of AMG 820 and have at least one PK sample collected.

Accumulation ratio is AUCtau following administration in Cycle 2 / AUCtau after administration in Cycle 1

Outcome measures

Measure	Part 1, Cohort 2: AMG 820 1100 mg + Pem 200 mg n=97 Participants Part 1 Cohort 2 includes participants with advanced solid tumors who were treated with 1100 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed.	Part 1, Cohort 1: AMG 820 1400 mg + Pem 200 mg n=18 Participants Part 1 Cohort 1 includes participants with advanced solid tumors who were treated with 1400 mg AMG 820 plus 200 mg pembrolizumab (Pem) every three weeks (Q3W) to determine safety. Participants could be treated up to 24 months if treatment was tolerable and clinical benefit was observed. If \>= 3 participants had dose limiting toxicities (DLTs), a second cohort was created with a lower AMG 820 dose + Pem 200 mg.	Part 2, Group 1: CRC MMR-proficient Group 1 is comprised of participants with colorectal cancer (CRC) who are proficient in mismatch repair genes (MMR). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 2: Pancreatic Cancer Group 2 is comprised of participants with advanced pancreatic cancer who are naïve to anti programmed-death 1 (PD-1), anti PD-ligand 1 (PD-L1), colony stimulating factor 1 (CSF-1) and colony stimulating factor 1 receptor (CSF-1R) therapies. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 3: NSCLC PD-L1 Low, Naïve Group 3 is comprised of participants with non-small cell lung cancer (NSCLC) who have low (\< 50%) tumor PD-L1- expression and are naïve to anti-PD-1/PD-L1/CSF-1/CSF-1R agents. AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4a: Refractory / Relapsing NSCLC PD-L1 Low Group 4a is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have low PD-L1 tumor expression (\<50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.	Part 2, Group 4b: Refractory/Relapsing NSCLC PD-L1 High Group 4b is comprised of participants who did not respond to or who relapsed during monotherapy with anti-PD-1/PD-L1 agents and are anti-CSF-1/CSF-1R naïve. These participants have high PD-L1 tumor expression (\>=50%). AMG 820 was administered at the recommended dose of 1100 mg intravenously in combination with pembrolizumab 200 mg every 3 weeks (± 3 days). Each group in Part 2 was evaluated separately using a Simon 2-stage design. Treatment continued until confirmed disease progression per modified irRECIST, or intolerance of study treatment, or clinically significant deterioration of health status requiring discontinuation, whichever occurred first, or the subject withdrew consent.
AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR)	1.23 ratio Geometric Coefficient of Variation 18	1.25 ratio Geometric Coefficient of Variation 16	—	—	—	—	—

Adverse Events

AMG 820 1100 MG

Serious events: 70 serious events

Other events: 97 other events

Deaths: 12 deaths

AMG 820 1400 MG

Serious events: 10 serious events

Other events: 18 other events

Deaths: 1 deaths

Serious adverse events

Measure	AMG 820 1100 MG n=98 participants at risk Includes participants from all treatment arms that were administered AMG 820 1100 mg.	AMG 820 1400 MG n=18 participants at risk Includes participants from all treatment arms that were administered AMG 820 1400 mg.
Blood and lymphatic system disorders Anaemia	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Blood and lymphatic system disorders Febrile neutropenia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Cardiac disorders Atrial flutter	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Cardiac disorders Cardiac arrest	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Cardiac disorders Cardiac failure congestive	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Cardiac disorders Pericardial effusion	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Periorbital oedema	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Uveitis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Abdominal pain	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Abdominal pain upper	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Autoimmune pancreatitis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Colitis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Diarrhoea	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Duodenal perforation	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Enterovesical fistula	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Ileus	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Nausea	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Obstruction gastric	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Proctalgia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Small intestinal obstruction	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Vomiting	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Asthenia	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Fatigue	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Malaise	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Non-cardiac chest pain	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Oedema peripheral	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Pyrexia	8.2% 8/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Autoimmune hepatitis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Bile duct obstruction	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Biliary colic	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Cholecystitis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Hepatitis	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Immune-mediated hepatitis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Abdominal infection	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Bacteraemia	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Cellulitis	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Clostridium difficile infection	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Cystitis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Device related infection	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Endocarditis staphylococcal	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Influenza	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Klebsiella bacteraemia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Liver abscess	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Lower respiratory tract infection	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Lung infection	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Pelvic abscess	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Pneumonia	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Pneumonia bacterial	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Sepsis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Septic shock	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Staphylococcal sepsis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Urinary tract infection	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Urosepsis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Alanine aminotransferase increased	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Aspartate aminotransferase increased	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Blood alkaline phosphatase increased	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Hepatic enzyme increased	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Transaminases increased	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Diabetes mellitus	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Failure to thrive	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypercalcaemia	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hyperkalaemia	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypoalbuminaemia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypokalaemia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hyponatraemia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypophosphataemia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Back pain	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer metastatic	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour flare	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Cerebellar infarction	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Cerebrovascular accident	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Dizziness	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Embolic cerebral infarction	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Encephalopathy	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Epilepsy	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Product Issues Device dislocation	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Psychiatric disorders Mental status changes	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Acute kidney injury	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Haematuria	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Nephritis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Nephrotic syndrome	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Renal haemorrhage	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Urinary tract obstruction	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Pharyngeal inflammation	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.1% 4/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Erythema nodosum	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Rash	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Rash generalised	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Rash maculo-papular	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.

Other adverse events

Measure	AMG 820 1100 MG n=98 participants at risk Includes participants from all treatment arms that were administered AMG 820 1100 mg.	AMG 820 1400 MG n=18 participants at risk Includes participants from all treatment arms that were administered AMG 820 1400 mg.
Skin and subcutaneous tissue disorders Pruritus	19.4% 19/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	22.2% 4/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Rash	25.5% 25/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Blood and lymphatic system disorders Anaemia	35.7% 35/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	22.2% 4/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Cardiac disorders Bradycardia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Endocrine disorders Hypothyroidism	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Endocrine disorders Parathyroid disorder	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Periorbital oedema	38.8% 38/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	55.6% 10/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Periorbital swelling	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Photophobia	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Uveitis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Vision blurred	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Eye disorders Visual impairment	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Abdominal distension	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Abdominal pain	20.4% 20/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	33.3% 6/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Ascites	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Constipation	22.4% 22/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	50.0% 9/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Diarrhoea	23.5% 23/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Dry mouth	8.2% 8/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	16.7% 3/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Dyspepsia	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Dysphagia	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Flatulence	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Nausea	26.5% 26/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	38.9% 7/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Oral pain	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Proctalgia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Rectal haemorrhage	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Stomatitis	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Gastrointestinal disorders Vomiting	12.2% 12/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Asthenia	8.2% 8/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Chills	11.2% 11/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	16.7% 3/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Face oedema	14.3% 14/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Fatigue	53.1% 52/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	55.6% 10/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Hyperthermia malignant	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Oedema	4.1% 4/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Oedema peripheral	10.2% 10/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Pain	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
General disorders Pyrexia	25.5% 25/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	16.7% 3/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Hepatotoxicity	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Hepatobiliary disorders Portal vein thrombosis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Bacteraemia	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Candida infection	8.2% 8/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Conjunctivitis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Lower respiratory tract infection	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Lung infection	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Mucosal infection	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Oral candidiasis	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Skin infection	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Upper respiratory tract infection	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Urinary tract infection	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Infections and infestations Viral infection	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Activated partial thromboplastin time prolonged	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Alanine aminotransferase	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Alanine aminotransferase increased	21.4% 21/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	22.2% 4/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Amylase increased	19.4% 19/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Aspartate aminotransferase abnormal	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Aspartate aminotransferase increased	59.2% 58/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	66.7% 12/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Blood alkaline phosphatase increased	13.3% 13/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Blood bilirubin increased	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Blood creatine phosphokinase increased	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Blood lactate dehydrogenase increased	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations International normalised ratio increased	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Lipase increased	18.4% 18/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Liver function test abnormal	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Lymphocyte count decreased	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Transaminases increased	7.1% 7/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Troponin increased	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations Weight decreased	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Investigations White blood cell count decreased	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Decreased appetite	22.4% 22/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	50.0% 9/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Dehydration	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hyperglycaemia	4.1% 4/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hyperlipasaemia	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hyperuricaemia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypoalbuminaemia	11.2% 11/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypocalcaemia	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypokalaemia	9.2% 9/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	16.7% 3/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypomagnesaemia	10.2% 10/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hyponatraemia	12.2% 12/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Hypophosphataemia	18.4% 18/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	44.4% 8/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Ketoacidosis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Metabolism and nutrition disorders Vitamin D deficiency	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Arthralgia	9.2% 9/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Back pain	10.2% 10/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Muscular weakness	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.1% 7/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Myalgia	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Musculoskeletal and connective tissue disorders Myopathy	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	16.7% 3/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer metastatic	4.1% 4/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	9.2% 9/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	22.2% 4/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Akathisia	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Aphasia	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Dizziness	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Dysgeusia	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Facial paresis	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Headache	11.2% 11/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Lethargy	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Psychiatric disorders Anxiety	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	11.1% 2/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Psychiatric disorders Confusional state	6.1% 6/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Psychiatric disorders Insomnia	4.1% 4/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	22.2% 4/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Bladder spasm	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Haematuria	7.1% 7/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Nephrotic syndrome	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Proteinuria	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Renal and urinary disorders Urinary retention	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Cough	19.4% 19/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.4% 22/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	16.7% 3/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Hiccups	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.1% 3/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Respiratory, thoracic and mediastinal disorders Pleural effusion	9.2% 9/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Dry skin	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Rash maculo-papular	14.3% 14/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	27.8% 5/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Vascular disorders Deep vein thrombosis	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Vascular disorders Embolism	2.0% 2/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Vascular disorders Hypertension	16.3% 16/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	22.2% 4/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Vascular disorders Hypotension	5.1% 5/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	0.00% 0/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.
Vascular disorders Venous thrombosis	1.0% 1/98 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.	5.6% 1/18 • The TEAE timeframe was Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2. The median time frame is 122 days. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. All adverse events (AEs) and disease related events (DREs) are integrated in above summaries.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: medinfo@amgen.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER