Trial results for a Phase 2 study (NCT04524689) investigating pembrolizumab in combination with tusamitamab ravtansine and chemotherapy for non-squamous non-small-cell lung cancer (NSQ NSCLC) were posted on ClinicalTrials.gov on 2025-03-17. The study was terminated, with results showing a 0% objective response rate (ORR) in one combination arm, while other arms achieved ORRs as high as 66.7%.
Background
Pembrolizumab (Keytruda) is an immunotherapy drug. The trial investigated its use in non-squamous non-small-cell lung cancer (NSQ NSCLC), a type of lung cancer.
Trial design
The Phase 2 study (NCT04524689) was titled "Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With NSQ NSCLC." The trial was terminated and enrolled 57 participants with non-squamous non-small-cell lung cancer (NSQ NSCLC). The study investigated combinations of tusamitamab ravtansine (SAR408701) with pembrolizumab, and tusamitamab ravtansine with pembrolizumab plus platinum-based chemotherapy (cisplatin or carboplatin) with or without pemetrexed. Its objectives included assessing tolerability, determining recommended doses, and evaluating antitumor activity.
Key results
The trial reported on dose-limiting toxicities (DLTs), objective response rates (ORR), and treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs).
For DLTs:
- In the Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab arm, 0 participants experienced study drug-related DLTs.
- In the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab arm, 0 participants experienced study drug-related DLTs.
- In the Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin arm, 0 participants experienced study drug-related DLTs.
- In the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin arm, 0 participants experienced study drug-related DLTs.
- In the Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed arm, 0 participants experienced study drug-related DLTs.
- In the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed arm, 1 participant experienced study drug-related DLTs.
For Objective Response Rate (ORR):
- In the Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab doublet cohort, the ORR was 47.8%.
- In the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab doublet cohort, the ORR was 0%.
- In the Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed quadruplet cohort, the ORR was 59.1%.
- In the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab + Cisplatin/Carboplatin + Pemetrexed quadruplet cohort, the ORR was 66.7%.
For Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs):
- In the Tusamitamab Ravtansine 150 mg/m^2 + Pembrolizumab arm, 23 participants experienced TEAEs and TESAEs.
- In the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab arm, 2 participants experienced TEAEs and TESAEs.
What this means
The results from this Phase 2 trial present a mixed picture for the combination of pembrolizumab with tusamitamab ravtansine and chemotherapy in NSQ NSCLC. While most arms showed a favorable tolerability profile with 0 reported dose-limiting toxicities, the objective response rates varied significantly. The 0% ORR observed in the Tusamitamab Ravtansine 170 mg/m^2 + Pembrolizumab arm is a notable finding, contrasting with ORRs up to 66.7% in other quadruplet cohorts. The termination of the study suggests that the overall benefit-risk profile or specific efficacy targets were not met, despite some promising ORR figures in certain combination regimens.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04524689, titled "Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With NSQ NSCLC," were posted on 2025-03-17 on clinicaltrials.gov.