Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
The study was a phase 2 multi-cohort, non-randomized, open-label, multi-center study assessing the clinical benefit of SAR444245 combined with other anticancer therapies for the treatment of participants aged 18 years and older with HNSCC. This study was structured as a master protocol for the investigation of SAR444245 with other anticancer therapies. Substudy 1-Cohort A1 aimed to establish proof-of-concept that SAR444245 combined with the anti-PD1 antibody pembrolizumab, will result in a significant increase in the observed number of objective responses in trial participants with HNSCC who were treatment-naïve for recurrent and/or metastatic (R/M) disease. Substudy 4-Cohort B1 aimed to establish proof-of-concept that SAR444245 combined with the anti-PD1 antibody pembrolizumab, will result in a significant increase in the observed number of objective responses in trial participants with HNSCC who have received treatment with PD1/PD-L1 and platinum-based regimen. Substudy 5-Cohort B2 aimed to establish proof-of-concept that SAR444245 combined with cetuximab will result in a significant increase in the observed number of objective responses in trial participants with HNSCC previously treated with platinum-based regimen & cetuximab-naive after failure of no more than 2 regimens for recurrent and/or metastatic (R/M) disease.
Detailed description
The duration of the study for an individual participant started from the signature of the main informed consent and included: * a screening period of up to 28 days * a treatment period \[max 35 cycles {cohort A1 and B1} = 735 days or until PD {cohort B2}\]; max 35 cycles for SAR444245 and pembrolizumab\] * an end-of-treatment visit at least approximately 30 days following the last administration of study drug (or until the participant received another anticancer therapy, whichever was earlier) * and a follow-up visits 3 months after treatment discontinuation and every 3 months thereafter following, until disease progression, or initiation of another antitumor treatment, or death, whichever was earlier
Interventions
DRUGPembrolizumab
Pharmaceutical Form: Concentration for solution for infusion Route of Administration: Intravenous Infusion
DRUGSAR444245 (Thor-707)
Pharmaceutical Form: Concentrate for solution for infusion Route of Administration: Intravenous Infusion
DRUGCetuximab
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous Infusion
Sponsors
Merck Sharp & Dohme LLC
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
-Participants were ≥ 18 years of age inclusive, at the time of signing the informed consent * Histologically or cytologically confirmed diagnosis of R/M HNSCC that was considered not amenable to further therapy with curative intent. The eligible primary tumor locations were oropharynx, oral cavity, hypopharynx, and larynx (nasopharynx is excluded). * Measurable disease. * Baseline biopsy was submitted for all cohort A1 Core Phase participants. * Baseline biopsy was submitted for all cohort B1, B2 Expansion Phase participants. * Known HPV p16 status for oropharyngeal cancer. * Participant agreed to follow protocol-specified contraception guidelines.
Exclusion criteria
-Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 * Had received prior IL2-based anticancer treatment. -For participants in Cohort A1: Prior treatment with an agent (approved or investigational) that blocks the PD-1/PD-L1 pathway (participants who joined a study with an anti-PD-1/PD-L1 in the experimental arm but have written confirmation they have not received anti-PD-1/PD-L1 are allowed). * For participants in Cohort B2: Prior treatment with cetuximab (prior cetuximab allowed if used for the treatment of locally advanced disease, with no progressive disease for at least 4 months from completion of prior cetuximab therapy). * For participants in Cohort B2: Electrolytes (magnesium, calcium, potassium) outside the normal ranges. * Participants under anti-hypertensive treatment who cannot temporarily (for at least 36 hours) withhold antihypertensive medications prior to each IMP dosing. * Participants with baseline SpO2 ≤92% (without oxygen therapy). * Comorbidity requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 2 weeks of IMP initiation. Inhaled or topical steroids are permitted, provided that they were not for treatment of an autoimmune disorder. Participants who require a brief course of steroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) were not excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A1: Objective Response Rate (ORR) | From first dose of study treatment administration (Day 1) up to approximately 21 months | 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. |
| Cohort B1: Objective Response Rate | From first dose of study treatment administration (Day 1) up to approximately 21 months | 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. |
| Cohort B2: Objective Response Rate | From first dose of study treatment administration (Day 1) up to approximately 21 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cohorts: Clinical Benefit Rate (CBR) | 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) | 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. |
| All Cohorts: Progression-Free Survival (PFS) | 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) | 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). |
| All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | 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) | 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. |
| All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin | 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) | 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. |
| Plasma Concentration of Pegenzileukin | Cycle 1 Day 2 (each cycle is 21 days) | Blood samples were collected at specified timepoints for the assessment of plasma concentration of pegenzileukin. |
| All Cohorts: Time to Response (TTR) | 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) | 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. |
| All Cohorts: Duration of Response (DOR) | 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). |
Countries
Argentina, Canada, Chile, France, Germany, Italy, Netherlands, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy 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. | 20 |
| 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. | 20 |
| 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. | 19 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse event: Not related to Coronavirus Disease 2019 (COVID-19) | 4 | 3 | 3 |
| Overall Study | Not related to COVID-19 | 2 | 0 | 0 |
| Overall Study | Progressive disease | 11 | 15 | 14 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | Total |
|---|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 11.4 | 61.9 years STANDARD_DEVIATION 8.8 | 58.8 years STANDARD_DEVIATION 11.4 | 59.5 years STANDARD_DEVIATION 10.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 1 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 9 Participants | 1 Participants | 12 Participants |
| Race (NIH/OMB) White | 12 Participants | 10 Participants | 12 Participants | 34 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 4 Participants | 10 Participants |
| Sex: Female, Male Male | 18 Participants | 16 Participants | 15 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 20 | 13 / 20 | 10 / 19 |
| other Total, other adverse events | 20 / 20 | 18 / 20 | 19 / 19 |
| serious Total, serious adverse events | 11 / 20 | 11 / 20 | 8 / 19 |
Outcome results
Primary
Cohort A1: Objective Response Rate (ORR)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | Cohort A1: Objective Response Rate (ORR) | 25.0 percentage of participants |
Primary
Cohort B1: Objective Response Rate
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | Cohort B1: Objective Response Rate | 0 percentage of participants |
Primary
Cohort B2: Objective Response Rate
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | Cohort B2: Objective Response Rate | 15.8 percentage of participants |
Secondary
All Cohorts: Clinical Benefit Rate (CBR)
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Clinical Benefit Rate (CBR) | 30.0 percentage of participants |
| Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | All Cohorts: Clinical Benefit Rate (CBR) | 0 percentage of participants |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Clinical Benefit Rate (CBR) | 21.1 percentage of participants |
Secondary
All Cohorts: Duration of Response (DOR)
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).
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Duration of Response (DOR) | 5.0 months |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Duration of Response (DOR) | 4.2 months |
Secondary
All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin
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.
Time frame: 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 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin | 2 Participants |
| Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin | 3 Participants |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Number of Participants With Anti-Drug Antibodies (ADAs) Against Pegenzileukin | 2 Participants |
Secondary
All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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.
Time frame: 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).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 20 Participants |
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 11 Participants |
| Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 20 Participants |
| Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 11 Participants |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 8 Participants |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 19 Participants |
Secondary
All Cohorts: Progression-Free Survival (PFS)
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).
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Progression-Free Survival (PFS) | 3.7 months |
| Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | All Cohorts: Progression-Free Survival (PFS) | 1.9 months |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Progression-Free Survival (PFS) | 4.0 months |
Secondary
All Cohorts: Time to Response (TTR)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | All Cohorts: Time to Response (TTR) | 4.1 months |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | All Cohorts: Time to Response (TTR) | 2.1 months |
Secondary
Plasma Concentration of Pegenzileukin
Blood samples were collected at specified timepoints for the assessment of plasma concentration of pegenzileukin.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CohortA1:R/M HNSCC Treatment-naïve for R/M Disease:Pegenzileukin 24mcg/kg+Pembrolizumab as 1LTherapy | Plasma Concentration of Pegenzileukin | 173.0 nanograms per milliliter | Standard Deviation 34.6 |
| Cohort B1: R/M HNSCC: Pegenzileukin 24 mcg/kg + Pembrolizumab as 2/3L Therapy | Plasma Concentration of Pegenzileukin | 173.7 nanograms per milliliter | Standard Deviation 55.5 |
| Cohort B2: R/M HNSCC: Pegenzileukin 24 mcg/kg + Cetuximab as 2/3L Therapy | Plasma Concentration of Pegenzileukin | 188.8 nanograms per milliliter | Standard Deviation 48.3 |