E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Squamous cell carcinoma of head and neck |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060121 |
E.1.2 | Term | Squamous cell carcinoma of head and neck |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the antitumor activity of SAR444245 in combination with other anti-cancer therapies in patients with HNSCC |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety profile of SAR444245 when combined with other anti-cancer therapies - To assess other indicators of antitumor activity - To assess the concentrations of SAR444245 - To assess the immunogenicity of SAR444245 - To confirm the dose of SAR444245 when combined with cetuximab and pembrolizumab (Substudy 02 Cohort A2) - To assess the concentrations of cetuximab (Substudy 02 - Cohort A2 and Substudy 05 - Cohort B2) |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Sub-study 01: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treatment-naïve participants for R/M disease, programmed cell death-ligand 1 (PD-L1) combined positive score as for S02 PD-L1 CPS ≥1 Protocol number: ACT16903-S01, version 1 dated on 2021-08-19
Sub-study 02: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab and cetuximab for the treatment of recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treatment-naïve participants for R/M disease, programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 Protocol number: ACT16903-S02, version 1 dated on 2021-08-19
Sub-study 04: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with pembrolizumab for the treatment of participants in 2nd/3rd line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) Protocol number: ACT16903-S04, version 1 dated on 2021-08-19
Sub-study 05: A Phase 2 non-randomized, open-label, multi-cohort, multi-center study assessing the clinical benefit of SAR444245 (THOR-707) combined with cetuximab for the treatment of cetuximab naïve participants in 2nd/3rd line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) Protocol number: ACT16903-S05, version 1 dated on 2021-08-19
For related objectives, refer to E.2.1 and E.2.2. |
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E.3 | Principal inclusion criteria |
- Participants must be ≥ 18 years of age inclusive, at the time of signing the informed consent - Histologically or cytologically confirmed diagnosis of R/M HNSCC that is considered not amenable to further therapy with curative intent. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx (nasopharynx is excluded) - Measurable disease - Baseline biopsy must be submitted for all cohort A1, A2 Core Phase participants - Baseline biopsy must be submitted for all cohort B1, B2 Expansion Phase participants - Known HPV p16 status for oropharyngeal cancer - Participant agrees to follow protocol-specified contraception guidelines |
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E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply: - Eastern Cooperative Oncology Group (ECOG) performance status of ≥2 - Has received prior IL2-based anticancer treatment - For participants in Cohorts A1, A2: 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 Cohorts A2, 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 Cohorts A2, 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 are 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) are not excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 9 months after the last participant receive first dose |
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E.5.2 | Secondary end point(s) |
1 - To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (TEAEs) 2 - To assess the safety profile of SAR444245 when combined with other anti-cancer therapies (SAEs) 3 - Time to response 4 - Duration of response (DoR) 5 - Clinical benefit rate (CBR) 6 - Progression free survival (PFS) 7 - To assess the concentrations of SAR444245 8 - To assess the immunogenicity of SAR444245 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-From first IMP dose up to 30 days after the last dose of IMP 2-From first IMP dose up to 90 days after the last dose of IMP 3,4,6-From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months 5-Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 9 months after the last participant receive first dose 7-At Day 1 and Day 15 of Cycle 1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days), maximum is up to approximately 24 months 8-At Day 1 and Day 15 of Cycle 1, at Day 1 of Cycle 2-4-7-10 + every 5th cycle (each cycle is 21 days) and 30 days after last IMP administration, maximum is up to approximately 24 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Korea, Republic of |
Taiwan |
United States |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |