Trial Outcomes & Findings for A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204) (NCT NCT05061420)

Last Updated: 2025-09-22

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

TERMINATED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

From first dose of study treatment administration (Day 1) up to approximately 21 months

Results posted on

2025-09-22

Participant Flow

This study was conducted at 27 centers (corresponds to number of site which screened at least one participant) in 12 countries. Out of 91 participants who were screened from 08 October 2021 to 21 October 2022, a total of 59 participants were enrolled in the study and were assigned to 1 of the 3 cohorts (Cohorts A1, B1 and B2) based on their disease type.

The study was terminated based on strategic sponsor decision not driven by any safety concerns. Cohort A2 was not initiated and no participants were enrolled. Note: Reason for not completed = Reason for permanent full intervention discontinuation.

Participant milestones

Participant milestones
Measure	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy Participants with head and neck squamous cell carcinoma (HNSCC) who were treatment-naïve for recurrent and/or metastatic (R/M) disease with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) \>=1 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 first line \[1L\] therapy), until disease progression (PD), unacceptable adverse event (AE), other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with programmed cell death protein (PD1)/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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 second or third line \[2/3L\] therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
Overall Study STARTED	20	20	19
Overall Study COMPLETED	1	2	1
Overall Study NOT COMPLETED	19	18	18

Reasons for withdrawal

Reasons for withdrawal
Measure	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy Participants with head and neck squamous cell carcinoma (HNSCC) who were treatment-naïve for recurrent and/or metastatic (R/M) disease with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) \>=1 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 first line \[1L\] therapy), until disease progression (PD), unacceptable adverse event (AE), other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with programmed cell death protein (PD1)/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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 second or third line \[2/3L\] therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
Overall Study Adverse event: Not related to Coronavirus Disease 2019 (COVID-19)	4	3	3
Overall Study Progressive disease	11	15	14
Overall Study Withdrawal by Subject	2	0	1
Overall Study Not related to COVID-19	2	0	0

Baseline Characteristics

A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=19 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.	Total n=59 Participants Total of all reporting groups
Age, Continuous	58.0 years STANDARD_DEVIATION 11.4 • n=99 Participants	61.9 years STANDARD_DEVIATION 8.8 • n=107 Participants	58.8 years STANDARD_DEVIATION 11.4 • n=206 Participants	59.5 years STANDARD_DEVIATION 10.5 • n=7 Participants
Sex: Female, Male Female	2 Participants n=99 Participants	4 Participants n=107 Participants	4 Participants n=206 Participants	10 Participants n=7 Participants
Sex: Female, Male Male	18 Participants n=99 Participants	16 Participants n=107 Participants	15 Participants n=206 Participants	49 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	6 Participants n=99 Participants	1 Participants n=107 Participants	6 Participants n=206 Participants	13 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) White	12 Participants n=99 Participants	10 Participants n=107 Participants	12 Participants n=206 Participants	34 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	9 Participants n=107 Participants	1 Participants n=206 Participants	12 Participants n=7 Participants

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to approximately 21 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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
Cohort A1: Objective Response Rate (ORR)	25.0 percentage of participants Interval 10.4 to 45.6	—	—

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to approximately 21 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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
Cohort B1: Objective Response Rate	0 percentage of participants Interval 0.0 to 13.9	—	—

PRIMARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to approximately 21 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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=19 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
Cohort B2: Objective Response Rate	15.8 percentage of participants Interval 4.4 to 35.9	—	—

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 28 months (Cohort A1), 27 months (Cohort B1) and 26 months (Cohort B2)

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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=19 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	20 Participants	20 Participants	19 Participants
All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	11 Participants	11 Participants	8 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=5 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=3 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
All Cohorts: Time to Response (TTR)	4.1 months Interval 2.0 to 7.0	—	2.1 months Interval 2.0 to 15.0

SECONDARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=5 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=3 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
All Cohorts: Duration of Response (DOR)	5.0 months Interval 3.9 to NA indicates that the upper limit of 90% confidence interval (CI) was not estimable due to insufficient number of participants with events.	—	4.2 months Interval 4.2 to NA indicates that the upper limit of 90% CI was not estimable due to insufficient number of participants with events.

SECONDARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

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 \<10mm (\<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	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=19 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
All Cohorts: Clinical Benefit Rate (CBR)	30.0 percentage of participants Interval 14.0 to 50.8	0 percentage of participants Interval 0.0 to 13.9	21.1 percentage of participants Interval 7.5 to 41.9

SECONDARY outcome

Timeframe: From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 27 months (Cohort A1), 26 months (Cohort B1) and 25 months (Cohort B2)

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).

Outcome measures

Outcome measures
Measure	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=19 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
All Cohorts: Progression-Free Survival (PFS)	3.7 months Interval 2.0 to 6.9	1.9 months Interval 1.8 to 2.0	4.0 months Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: Cycle 1 Day 2 (each cycle is 21 days)

Population: The pharmacokinetic (PK) population included all participants from exposed population with at least one PK concentration available after the first dose of study treatment.

Blood samples were collected at specified timepoints for the assessment of plasma concentration of pegenzileukin.

Outcome measures

Outcome measures
Measure	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=14 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=19 Participants Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=16 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
Plasma Concentration of Pegenzileukin	173.0 nanograms per milliliter Standard Deviation 34.6	173.7 nanograms per milliliter Standard Deviation 55.5	188.8 nanograms per milliliter Standard Deviation 48.3

SECONDARY outcome

Population: The ADA population included all participants from exposed population with at least one ADA result (positive, negative or inconclusive) after the first dose of study treatment.

Blood samples were collected at specified timepoints to assess the presence of ADAs against pegenzileukin. Treatment-emergent ADA was defined as at least one treatment-induced or treatment-boosted ADA. Treatment-induced ADA was defined as ADA that developed during the TE period and without pre-existing ADA (including participants without pre-treatment samples). Treatment-boosted ADA was defined as pre-existing ADA that was boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADA are presented.

Outcome measures

Outcome measures
Measure	CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy n=20 Participants Participants with HNSCC who were treatment-naïve for R/M disease with PD-L1 CPS \>=1 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 1L therapy), until PD, unacceptable AE, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy n=20 Participants Participants with R/M HNSCC previously treated with PD1/PD-L1-based regimen and platinum-based regimen after failure of no more than 2 regimens for R/M disease 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, other full permanent discontinuation criteria was met or completion of Cycle 35.	Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy n=18 Participants Participants with R/M HNSCC previously treated with platinum-based regimen and cetuximab-naïve after failure of no more than 2 regimens for R/M disease 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 2/3L therapy) until PD.
All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin	2 Participants	3 Participants	2 Participants

Adverse Events

CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy

Serious events: 11 serious events

Other events: 20 other events

Deaths: 8 deaths

Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy

Serious events: 11 serious events

Other events: 18 other events

Deaths: 13 deaths

Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy

Serious events: 8 serious events

Other events: 19 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610 ext 6#

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER