Trial results for a Phase 2 study (NCT05061420) investigating pembrolizumab (Keytruda) in combination with SAR444245 for head and neck squamous cell carcinoma (HNSCC) were posted on ClinicalTrials.gov on 2025-09-22. The study found an objective response rate (ORR) of 25.0% in treatment-naïve recurrent/metastatic HNSCC participants receiving the combination as first-line therapy.
Background
Pembrolizumab is an anti-PD1 antibody. This study investigated its combination with SAR444245 (also known as pegenzileukin) for the treatment of participants with squamous cell carcinoma of the head and neck (HNSCC).
Trial design
The study (NCT05061420) was a Phase 2, multi-cohort, non-randomized, open-label, multi-center study that enrolled 59 participants with squamous cell carcinoma of the head and neck (HNSCC). The trial was structured as a master protocol to investigate SAR444245 with other anticancer therapies. The study was terminated. Substudy 1-Cohort A1 aimed to establish proof-of-concept for SAR444245 combined with pembrolizumab in increasing objective responses. The study included three main cohorts:
- Cohort A1: Recurrent/metastatic HNSCC treatment-naïve for R/M disease, receiving pegenzileukin 24 mcg/kg + pembrolizumab as first-line therapy.
- Cohort B1: Recurrent/metastatic HNSCC, receiving pegenzileukin 24 mcg/kg + pembrolizumab as second or third-line therapy.
- Cohort B2: Recurrent/metastatic HNSCC, receiving pegenzileukin 24 mcg/kg + cetuximab as second or third-line therapy.
Key results
The trial results presented objective response rates (ORR) and safety data across the different cohorts:
- For Cohort A1 (R/M HNSCC treatment-naïve for R/M disease, pegenzileukin 24 mcg/kg + pembrolizumab as first-line therapy), the Objective Response Rate (ORR) was 25.0%. The median Time to Response (TTR) for this cohort was 4.1 months, and the median Duration of Response (DOR) was 5.0 months.
- For Cohort B1 (R/M HNSCC, pegenzileukin 24 mcg/kg + pembrolizumab as second or third-line therapy), the Objective Response Rate (ORR) was 0%.
- For Cohort B2 (R/M HNSCC, pegenzileukin 24 mcg/kg + cetuximab as second or third-line therapy), the Objective Response Rate (ORR) was 15.8%. The median Time to Response (TTR) for this cohort was 2.1 months.
Regarding safety, the number of participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) were reported:
- In Cohort A1, 20 participants experienced TEAEs/TESAEs, with 11 experiencing serious adverse events.
- In Cohort B1, 20 participants experienced TEAEs/TESAEs, with 11 experiencing serious adverse events.
- In Cohort B2, 19 participants experienced TEAEs/TESAEs, with 8 experiencing serious adverse events.
What this means
The results from this Phase 2 study provide insights into the efficacy and safety of SAR444245 in combination with either pembrolizumab or cetuximab for HNSCC. The 25.0% ORR observed in treatment-naïve recurrent/metastatic HNSCC participants receiving SAR444245 + pembrolizumab as first-line therapy suggests potential activity in this setting. However, the 0% ORR for the same combination in second or third-line therapy indicates a lack of efficacy in previously treated patients. The trial's termination, along with these varied response rates, will inform future development strategies for SAR444245 in HNSCC.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05061420, titled "A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With HNSCC (Master Protocol) (Pegathor Head and Neck 204)," were posted on 2025-09-22 on clinicaltrials.gov.