Trial Outcomes & Findings for A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203) (NCT NCT05104567)

Last Updated: 2025-09-24

Results Overview

ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 millimeter (mm) (\<1 centimeter \[cm\]). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

138 participants

Primary outcome timeframe

From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months

Results posted on

2025-09-24

Participant Flow

This study was conducted at 29 centers (corresponds to number of site which screened at least one participant) in 9 countries. Out of 193 participants who were screened from 09 December 2021 to 26 October 2022, a total of 138 participants were enrolled in the study and were assigned to 1 of the 7 cohorts (Cohorts A, B1, B2, B3, C, D1 and D2) based on their disease type.

Note: Reason for not completed = Reason for permanent full intervention discontinuation.

Participant milestones

Participant milestones
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC), regardless of programmed cell death-ligand 1 (PD-L1) expression (any combined positive score \[CPS\]), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-programmed cell death-1 (PD-1)/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 microgram per kilogram (mcg/kg) along with pembrolizumab 200 milligram (mg) via intravenous (IV) infusion every 3 weeks (q3w) on Day 1 of each cycle (each cycle is 21 days) (as second-line or third-line \[2/3L\] therapy), until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy Participants with advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 \& 3 gastro-esophageal junction adenocarcinoma (GEJ) and for whom standard of care (SOC) was not in best interest or where no SOC was established, non-high-level microsatellite instability (MSI-H) disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \>=1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as first to \[1-\]3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS <1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-fourth \[4\]L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic hepatocellular carcinoma (HCC), regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least stable disease (SD) as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic colorectal cancer (CRC), regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-sixth \[6\]L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/square meter (m\^2) on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
Overall Study STARTED	5	22	19	18	20	30	24
Overall Study COMPLETED	0	1	0	0	0	0	0
Overall Study NOT COMPLETED	5	21	19	18	20	30	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC), regardless of programmed cell death-ligand 1 (PD-L1) expression (any combined positive score \[CPS\]), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-programmed cell death-1 (PD-1)/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 microgram per kilogram (mcg/kg) along with pembrolizumab 200 milligram (mg) via intravenous (IV) infusion every 3 weeks (q3w) on Day 1 of each cycle (each cycle is 21 days) (as second-line or third-line \[2/3L\] therapy), until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy Participants with advanced unresectable or metastatic gastric cancer (GC) or Siewert Type 2 \& 3 gastro-esophageal junction adenocarcinoma (GEJ) and for whom standard of care (SOC) was not in best interest or where no SOC was established, non-high-level microsatellite instability (MSI-H) disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \>=1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as first to \[1-\]3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS <1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-fourth \[4\]L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic hepatocellular carcinoma (HCC), regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least stable disease (SD) as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic colorectal cancer (CRC), regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-sixth \[6\]L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/square meter (m\^2) on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
Overall Study Adverse event: Related to Coronavirus Disease 2019 (COVID-19)	0	1	0	0	0	0	0
Overall Study Adverse event: Not related to COVID-19	0	5	3	1	3	2	0
Overall Study Progressive disease	3	13	13	17	17	28	24
Overall Study Withdrawal by Subject	1	1	2	0	0	0	0
Overall Study Other	1	1	1	0	0	0	0

Baseline Characteristics

A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=5 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB1:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS>=1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy n=22 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \>=1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24mcg/kg+Pembrolizumab as 1-3LTherapy n=19 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=18 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy n=30 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy n=24 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.	Total n=138 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 4.4 • n=5 Participants	58.1 years STANDARD_DEVIATION 10.3 • n=7 Participants	56.5 years STANDARD_DEVIATION 13.1 • n=5 Participants	58.3 years STANDARD_DEVIATION 10.9 • n=4 Participants	65.7 years STANDARD_DEVIATION 8.8 • n=21 Participants	62.7 years STANDARD_DEVIATION 12.1 • n=8 Participants	61.7 years STANDARD_DEVIATION 10.0 • n=8 Participants	60.8 years STANDARD_DEVIATION 11.0 • n=24 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	4 Participants n=4 Participants	6 Participants n=21 Participants	11 Participants n=8 Participants	7 Participants n=8 Participants	42 Participants n=24 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	17 Participants n=7 Participants	12 Participants n=5 Participants	14 Participants n=4 Participants	14 Participants n=21 Participants	19 Participants n=8 Participants	17 Participants n=8 Participants	96 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	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=8 Participants	4 Participants n=8 Participants	16 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	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	1 Participants n=24 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	10 Participants n=4 Participants	14 Participants n=21 Participants	30 Participants n=8 Participants	18 Participants n=8 Participants	103 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	2 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=8 Participants	1 Participants n=8 Participants	17 Participants n=24 Participants

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=5 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
Cohort A: Objective Response Rate (ORR)	20.0 percentage of participants Interval 1.0 to 65.7	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 25 months

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

ORR was defined as the percentage of participants who had a confirmed CR or PR as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=22 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy n=19 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=18 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
Cohorts B1, B2 and B3: Objective Response Rate	13.6 percentage of participants Interval 3.8 to 31.6	5.3 percentage of participants Interval 0.3 to 22.6	11.1 percentage of participants Interval 2.0 to 31.0	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 20 months

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
Cohort C: Objective Response Rate	5.0 percentage of participants Interval 0.3 to 21.6	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=30 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy n=24 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
Cohorts D1 and D2: Objective Response Rate	0 percentage of participants Interval 0.0 to 9.5	8.3 percentage of participants Interval 1.5 to 24.0	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to 30 days post last dose of study treatment administration, up to approximately 9 months (Cohorts A, D1 and D2), 26 months (Cohorts B1, B2 and B3) and 21 months (Cohort C)

Population: The exposed population included all participants who had given their informed consent and received at least one dose of study treatment (pegenzileukin or other anticancer therapies).

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE was any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened (according to the Investigator's opinion) or became serious during the TE period.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=5 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy n=22 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=19 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=18 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy n=30 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy n=24 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	5 Participants	22 Participants	19 Participants	18 Participants	19 Participants	30 Participants	24 Participants
All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	2 Participants	17 Participants	13 Participants	9 Participants	7 Participants	19 Participants	11 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 8 months (Cohort A, D1 and D2), 25 months (Cohort B1, B2 and B3), 20 months (Cohort C)

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment. Only participants with confirmed CR or PR were analyzed.

TTR was defined as the time from the date of first study treatment administration to the first tumor assessment at which the overall response was recorded as PR or CR that was subsequently confirmed as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=1 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy n=3 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=1 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=2 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=1 Participants Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy n=2 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
All Cohorts: Time to Response (TTR)	1.9 months Standard Deviation NA NA indicates that the standard deviation (SD) was not estimable for 1 participant.	2.1 months Standard Deviation 0.2	4.2 months Standard Deviation NA NA indicates that the SD was not estimable for 1 participant.	3.0 months Standard Deviation 1.3	6.0 months Standard Deviation NA NA indicates that the SD was not estimable for 1 participant.	—	2.0 months Standard Deviation 0.1

SECONDARY outcome

DOR was defined as the time from the date of first tumor assessment at which the overall response was recorded as CR or PR that was subsequently confirmed to the date of first documentation of objective PD before the initiation of any post-treatment anti-cancer therapy or death due to any cause, whichever occurred first, as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=1 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy n=3 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=1 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=2 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=1 Participants Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy n=2 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
All Cohorts: Duration of Response (DOR)	NA months NA indicates that the median, upper and lower limit of 90% confidence interval (CI) were not estimable due to insufficient number of participants with events.	13.1 months NA indicates that the upper and lower limit of 90% CI were not estimable, as there were insufficient numbers of participants with 2/3 participants censored prior to any event.	NA months NA indicates that the median, upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	8.8 months Interval 8.6 to NA indicates that the upper limit of 90% CI was not estimable due to insufficient number of participants with events.	NA months NA indicates that the median, upper and lower limit of 90% CI were not estimable due to insufficient number of participants with events.	—	4.1 months Interval 4.1 to NA indicates that the upper limit of 90% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

CBR was defined as the percentage of participants with clinical benefit (confirmed CR or PR as best overall response \[BOR\], or SD lasting at least 6 months), as per RECIST v 1.1. CR was defined as the disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) with reduction in short axis to \<10 mm (\<1 cm). PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. BOR was defined as the best response recorded from the start of the study treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Outcome measures

Outcome measures
Measure	Cohort A: ESCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=5 Participants Participants with advanced unresectable or metastatic ESCC, regardless of PD-L1 expression (any CPS), who had received at least 1 but no more than 2 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1 based regimen were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	CohortB2:GC/GEJ PD-1/PD-L1 naïve Non-MSI-H CPS<1:Pegenzileukin24 mcg/kg+Pembrolizumab as 1-3LTherapy n=22 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had not received more than 2 prior lines of treatment that did not include an anti-PD-1/PD-L1-based regimen with the level of PD-L1 expression at baseline as CPS \<1 GC/GEJ were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 1-3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=19 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B3: GC/GEJ Post PD-1/PD-L1 Non-MSI-H: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2-4L Therapy n=18 Participants Participants with advanced unresectable or metastatic GC or Siewert Type 2 \& 3 GEJ and for whom SOC was not in best interest or where no SOC was established, non-MSI-H disease and had received atleast 1 and no more than 3 prior lines of treatment and had progressed after primary or secondary resistance to an anti-PD-1/PD-L1-based regimen (regardless of the disease CPS status) were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2-4L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort C: HCC Post PD-1/PD-L1: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with advanced unresectable or metastatic HCC, regardless of any CPS, who relapsed on prior PD-1/PD-L1-based regimens, with at least SD as best response and with no more than 2 prior lines of treatment were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 2/3L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D1: CRC Non-MSI-H Any RAS: Pegenzileukin 24 mcg/kg + Pembrolizumab as 3-6L Therapy n=30 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, any RAS type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg along with pembrolizumab 200 mg via IV infusion q3w on Day 1 of each cycle (each cycle is 21 days) (as 3-6L therapy), until PD, unacceptable AE or other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort D2: CRC Non-MSI-H RAS Wild Type: Pegenzileukin 24 mcg/kg + Cetuximab as 3-6L Therapy n=24 Participants Participants with advanced unresectable or metastatic CRC, regardless of any CPS, non-MSI-H disease, RAS wild type, who had progressed on prior regimens having contained fluoropyrimidine, oxaliplatin, irinotecan, with either bevacizumab or cetuximab, and with no more than 5 prior lines of treatments were included in this cohort. Participants received pegenzileukin 24 mcg/kg q3w on Day 1 of each cycle along with cetuximab as an initial loading dose of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 starting via IV infusion once weekly from Cycle 1 Day 8 (each cycle is 21 days) (as 3-6L therapy) until PD.
All Cohorts: Clinical Benefit Rate (CBR)	40.0 percentage of participants Interval 7.6 to 81.1	22.7 percentage of participants Interval 9.4 to 42.0	10.5 percentage of participants Interval 1.9 to 29.6	11.1 percentage of participants Interval 2.0 to 31.0	10.0 percentage of participants Interval 1.8 to 28.3	6.7 percentage of participants Interval 1.2 to 19.5	12.5 percentage of participants Interval 3.5 to 29.2

SECONDARY outcome

Population: The efficacy population included all participants from the exposed population with at least one evaluable post-baseline tumor assessment or who permanently discontinued study treatment.

PFS was defined as the time from the date of first study treatment to the date of the first documentation of objective PD or death due to any cause, whichever occurred first, as per RECIST v 1.1. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm (0.5 cm).