Trial results for a Phase 1/2 study (NCT04418661) investigating adagrasib in combination with vociprotafib for advanced malignancies were posted on ClinicalTrials.gov on 2025-04-20. The study, which also included pembrolizumab in other arms, was officially terminated, with safety and tolerability data now available.
Background
The study, titled "Safety and Efficacy Study of Vociprotafib (SAR442720) in Combination With Other Agents in Advanced Malignancies," explored the safety and efficacy of vociprotafib in combination with other agents. Specifically, adagrasib was investigated in combination with vociprotafib in participants with KRAS G12C NSCLC in Part 3A of the study, while pembrolizumab was combined with vociprotafib in other parts for advanced solid tumors.
Trial design
The Phase 1/2 study (NCT04418661) was designed as a safety and efficacy study. It enrolled 65 participants with metastatic neoplasm. The trial was officially terminated. The study's objectives included characterizing the safety and tolerability of vociprotafib in combination with pembrolizumab in advanced solid tumors, defining the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) for this combination, and determining its anti-tumor activity. For Part 3A, the objectives were to define the MTD and RP2D for the combination of vociprotafib and adagrasib in participants with KRAS G12C NSCLC and to characterize its safety and tolerability.
Key results
The trial results focused on safety, tolerability, and preliminary efficacy across different combination arms:
- For "Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)" in Part 1:
- In the SAR442720 140mg BIW + Pembrolizumab group, 4 participants experienced TEAEs and 0 participants experienced TESAEs.
- In the SAR442720 200mg BIW + Pembrolizumab group, 13 participants experienced TEAEs and 7 participants experienced TESAEs.
- For "Number of Participants With Treatment Related Dose Limiting Toxicities (DLTs)" across Parts 1 and 3A:
- In the SAR442720 140mg BIW + Pembrolizumab group, 0 participants experienced DLTs.
- In the SAR442720 200mg BIW + Pembrolizumab group, 2 participants experienced DLTs.
- In the SAR442720 100mg BIW + Adagrasib group (Part 3A), 0 participants experienced DLTs.
- For "Percentage of Participants With Objective Response Rate (ORR)" in Part 2:
- In the SAR442720 200mg + Pembrolizumab - Cohort A1 (PDL1 TPS >=50%), the ORR was 23.1% (90% Confidence Interval).
- In the SAR442720 200mg + Pembrolizumab - Cohort A2 (PDL1 TPS 1% - 49%), the ORR was 5.3% (90% Confidence Interval).
- For "Number of Participants With Treatment-Emergent Adverse Events and Treatment-Emergent Serious Adverse Events" in Part 3A:
- In the SAR442720 100mg BIW + Adagrasib group, 1 participant experienced TEAEs and 0 participants experienced TESAEs.
- For "Plasma Concentration of SAR442720 in Combination With Pembrolizumab" in Part 4:
- The mean plasma concentration was 0 ng/mL (Standard Deviation: 0).
What this means
The termination of this Phase 1/2 study suggests that the development of these specific combinations, particularly for vociprotafib with adagrasib or pembrolizumab, did not proceed as initially planned. The posted results provide safety and tolerability data, including the incidence of treatment-emergent adverse events and dose-limiting toxicities across various arms. For the vociprotafib and pembrolizumab combination, preliminary objective response rates were observed, with 23.1% in the PDL1 TPS >=50% cohort and 5.3% in the PDL1 TPS 1%-49% cohort. However, no efficacy data was reported for the adagrasib combination arm in the key measurements, only safety and DLTs, where 0 participants experienced DLTs and 1 participant experienced TEAEs in the SAR442720 100mg BIW + Adagrasib group.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04418661, titled "Safety and Efficacy Study of Vociprotafib (SAR442720) in Combination With Other Agents in Advanced Malignancies," were posted on 2025-04-20 on clinicaltrials.gov.