A Phase 2 Non-randomized, Open-label, Multi-cohort, Multi-center Study Assessing the Clinical Benefit of SAR444245 (THOR-707) Combined With Other Anticancer Therapies for the Treatment of Participants With Head and Neck Squamous Cell Carcinoma (HNSCC)
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Sponsor
- Sanofi
- Enrollment
- 59
- Locations
- 27
- Primary Endpoint
- Cohort A1: Objective Response Rate (ORR)
- Status
- Terminated
- Last Updated
- 7 months ago
Overview
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
Investigators
Eligibility Criteria
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.
Arms & Interventions
Cohort A1 (sub study 01) treatment- naïve
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.
Intervention: Pembrolizumab
Cohort A1 (sub study 01) treatment- naïve
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.
Intervention: SAR444245 (Thor-707)
Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments
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
Intervention: Pembrolizumab
Cohort B1: (sub study 04) PD1/PD-L1 and platinum-based treatments
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
Intervention: SAR444245 (Thor-707)
Cohort B2: (sub study 05) cetuximab- naïve
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.
Intervention: SAR444245 (Thor-707)
Cohort B2: (sub study 05) cetuximab- naïve
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.
Intervention: Cetuximab
Outcomes
Primary Outcomes
Cohort A1: Objective Response Rate (ORR)
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- 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))
- 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))
- 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))
- 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))
- 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))
- Plasma Concentration of Pegenzileukin(Cycle 1 Day 2 (each cycle is 21 days))
- 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))