Trial results for the Phase 2 study NCT05104567, investigating pembrolizumab (Keytruda) in combination with SAR444245 (Pegenzileukin) for various gastrointestinal cancers, were posted on ClinicalTrials.gov on 2025-07-01. The combination therapy achieved an objective response rate (ORR) of 20.0% in participants with esophageal squamous cell carcinoma (ESCC) who had prior PD-1/PD-L1 therapy.
Background
The study investigated SAR444245 (THOR-707), a non-alpha-IL2, combined with other anticancer therapies, including pembrolizumab, for the treatment of participants with advanced and metastatic gastrointestinal cancers. The master protocol design allowed for the investigation of this combination across multiple cohorts of patients with conditions such as oesophageal squamous cell carcinoma, gastric cancer, hepatocellular carcinoma, and colorectal cancer.
Trial design
The Pegathor Gastrointestinal 203 study (NCT05104567) was a Phase 2, non-randomized, open-label, multi-cohort, multi-center study. It enrolled 138 participants aged 18 years and older with advanced and metastatic gastrointestinal cancer, including oesophageal squamous cell carcinoma, gastric cancer, hepatocellular carcinoma, and colorectal cancer. The study assessed the clinical benefit of SAR444245 (THOR-707) combined with other anticancer therapies, such as pembrolizumab and cetuximab, across various cohorts.
Key results
The study reported objective response rates (ORR) for various cohorts:
- Cohort A (oesophageal squamous cell carcinoma (ESCC) post PD-1/PD-L1 therapy): ORR of 20.0% with Pegenzileukin 24 mcg/kg + Pembrolizumab.
- Cohort B1 (gastric/gastroesophageal junction (GC/GEJ) cancer, PD-1/PD-L1 naïve, non-MSI-H, CPS≥1): ORR of 13.6% with Pegenzileukin 24 mcg/kg + Pembrolizumab.
- Cohort B2 (GC/GEJ cancer, PD-1/PD-L1 naïve, non-MSI-H, CPS<1): ORR of 5.3% with Pegenzileukin 24 mcg/kg + Pembrolizumab.
- Cohort B3 (GC/GEJ cancer, post PD-1/PD-L1, non-MSI-H): ORR of 11.1% with Pegenzileukin 24 mcg/kg + Pembrolizumab.
- Cohort C (hepatocellular carcinoma (HCC) post PD-1/PD-L1 therapy): ORR of 5.0% with Pegenzileukin 24 mcg/kg + Pembrolizumab.
- Cohort D1 (colorectal cancer (CRC), non-MSI-H, any RAS): ORR of 0% with Pegenzileukin 24 mcg/kg + Pembrolizumab.
- Cohort D2 (CRC, non-MSI-H, RAS Wild Type): ORR of 8.3% with Pegenzileukin 24 mcg/kg + Cetuximab.
Safety data indicated the number of participants experiencing treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) in several cohorts: Cohort A reported 5 Participants, Cohort B1 had 22 Participants, Cohort B2 had 19 Participants, Cohort B3 had 18 Participants, and Cohort C had 19 Participants.
What this means
The results from the Phase 2 master protocol indicate varied objective response rates for SAR444245 in combination with pembrolizumab or cetuximab across different advanced gastrointestinal cancer cohorts. The highest ORR of 20.0% was observed in oesophageal squamous cell carcinoma patients who had previously received PD-1/PD-L1 therapy, suggesting potential benefit in this specific population. However, responses were lower or absent in other cohorts, particularly colorectal cancer with the pembrolizumab combination, highlighting the need for further investigation into patient selection and combination strategies for these indications.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05104567, titled "A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Gastrointestinal Cancer (Master Protocol) (Pegathor Gastrointestinal 203)," were posted on 2025-07-01 on clinicaltrials.gov.