Trial results for the Phase 2 study NCT04914897, investigating pembrolizumab in combination with SAR444245 for lung cancer and mesothelioma, were posted on ClinicalTrials.gov on 2025-10-02. The study was terminated, with objective response rates varying across cohorts, reaching 41.2% in first-line non-small cell lung cancer patients with PD-L1 TPS >=50%.
Background
Pembrolizumab (Keytruda) is an immune checkpoint inhibitor approved for various cancers. This Phase 2 study explored its combination with SAR444245 (Pegenzileukin), an investigational agent, in patients with non-small cell lung cancer (NSCLC) and pleural mesothelioma.
Trial design
The Phase 2 'Pegathor Lung 202' study (NCT04914897) was designed to determine the antitumor activity and assess the safety of SAR444245 combined with pembrolizumab. The trial enrolled 106 participants with pleural mesothelioma or non-small cell lung cancer and was ultimately terminated. It included cohorts for first-line NSCLC (PD-L1 TPS >=50% and 1%-49%) and second/third-line NSCLC and mesothelioma.
Key results
The trial evaluated Objective Response Rate (ORR) across different cohorts:
- For Cohort A1 (NSCLC, PD-L1 TPS >=50%, 1L therapy), the ORR was 41.2%.
- For Cohort A2 (NSCLC, PD-L1 TPS 1%-49%, 1L therapy), the ORR was 15.0%.
- For Cohort B1 (NSCLC, 2/3L therapy), the ORR was 2.5%.
- For Cohort C1 (Mesothelioma, 2/3L therapy), the ORR was 3.4%.
Safety data reported the number of participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs):
- Cohort A1: 16 participants with TEAEs, 6 with TESAEs.
- Cohort A2: 20 participants with TEAEs, 11 with TESAEs.
- Cohort B1: 40 participants with TEAEs, 21 with TESAEs.
- Cohort C1: 29 participants with TEAEs, 13 with TESAEs.
What this means
The termination of the Phase 2 study suggests that the combination of SAR444245 and pembrolizumab did not meet overall development objectives. While Cohort A1 (first-line NSCLC with high PD-L1 expression) showed an ORR of 41.2%, response rates were significantly lower at 2.5% in second/third-line NSCLC and 3.4% in mesothelioma, indicating limited efficacy in these populations. Safety data was also collected across all cohorts.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov. The results for study NCT04914897, titled 'A Study of SAR444245 Combined With Other Anticancer Therapies for the Treatment of Participants With Lung Cancer or Mesothelioma (Pegathor Lung 202),' were posted on 2025-10-02 on clinicaltrials.gov.