A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Interventions
- Registration Number
- NCT05061420
- Lead Sponsor
- Sanofi
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 59
-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.
-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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A1 (sub study 01) treatment- naïve Pembrolizumab Participants with HNSCC, who were treatment-naïve for R/M disease and have a PD-L1 Combined Positive Score (CPS) ≥1, received pembrolizumab followed by SAR444245. Both drugs administered by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles. Cohort A1 (sub study 01) treatment- naïve SAR444245 (Thor-707) Participants with HNSCC, who were treatment-naïve for R/M disease and have a PD-L1 Combined Positive Score (CPS) ≥1, received pembrolizumab followed by SAR444245. Both drugs administered by intravenous (IV) infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles. Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments Pembrolizumab Participants with HNSCC who received treatment with a PD1/PD-L1-based regimen \& platinum-based regimen and have failed no more than 2 regimens for R/M disease, received pembrolizumab followed by SAR444244. Both drugs administered IV infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments SAR444245 (Thor-707) Participants with HNSCC who received treatment with a PD1/PD-L1-based regimen \& platinum-based regimen and have failed no more than 2 regimens for R/M disease, received pembrolizumab followed by SAR444244. Both drugs administered IV infusion on Day 1 of each 21-day treatment cycle for up to 35 cycles Cohort B2: (sub study 05) cetuximab- naïve SAR444245 (Thor-707) Participants with R/M HNSCC, who were cetuximab-naïve, have received treatment with a platinum-based regimen, and have failed no more than 2 regimens for R/M disease, received treatment with cetuximab followed by SAR444245. Cetuximab IV was given on days 1, 8, and 15 of each 21 day. SAR444245 was administered by IV infusion on Day 1 of each 21-day treatment cycle. Dosing of both drugs continued until disease progression, unacceptable toxicity, or withdrawal of consent. Cohort B2: (sub study 05) cetuximab- naïve Cetuximab Participants with R/M HNSCC, who were cetuximab-naïve, have received treatment with a platinum-based regimen, and have failed no more than 2 regimens for R/M disease, received treatment with cetuximab followed by SAR444245. Cetuximab IV was given on days 1, 8, and 15 of each 21 day. SAR444245 was administered by IV infusion on Day 1 of each 21-day treatment cycle. Dosing of both drugs continued until disease progression, unacceptable toxicity, or withdrawal of consent.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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: 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).
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).
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: 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.
Trial Locations
- Locations (27)
City of Hope- Site Number : 8400007
🇺🇸Duarte, California, United States
University of Colorado- Site Number : 8400004
🇺🇸Aurora, Colorado, United States
University of Michigan- Site Number : 8400008
🇺🇸Ann Arbor, Michigan, United States
Thomas Jefferson University Hospital Site Number : 8400003
🇺🇸Philadelphia, Pennsylvania, United States
Seattle Cancer Care Alliance Site Number : 8400006
🇺🇸Seattle, Washington, United States
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 1240001
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 1520003
🇨🇱Santiago, Reg Metropolitana de Santiago, Chile
Investigational Site Number : 1520001
🇨🇱Santiago, Reg Metropolitana de Santiago, Chile
Investigational Site Number : 1520004
🇨🇱Viña del Mar, Región de Valparaíso, Chile
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