Merck and Moderna: Phase 3 INTerpath-001 shows intismeran plus KEYTRUDA improves RFS and DMFS in resected stage IIB–IV melanoma
- INTerpath-001 met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS).
- The trial evaluated intismeran autogene (V940/mRNA-4157), an individualized mRNA neoantigen therapy, combined with KEYTRUDA (pembrolizumab) versus KEYTRUDA alone in completely resected stage IIB–IV cutaneous melanoma patients with no prior systemic therapy.
- This is reported as the first positive Phase 3 readout for an individualized neoantigen therapy and for an mRNA-based cancer therapy, and the first Phase 3 to show a clinically meaningful improvement over KEYTRUDA alone in the adjuvant melanoma setting.
- Safety for the combination was consistent with prior studies with no new safety signals; the study will continue to evaluate overall survival (OS) and data will be presented at an upcoming international medical meeting and shared with regulators.
Topline results
At a pre-specified interim analysis, the Phase 3 INTerpath-001 trial met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS) for intismeran autogene combined with KEYTRUDA versus KEYTRUDA alone in patients with completely resected stage IIB, IIC, III or IV cutaneous melanoma who had not received prior systemic therapy.
Treatment and safety
Intismeran autogene (intismeran; V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy designed for each patient’s unique tumor mutations to train the immune system. The combination with pembrolizumab showed safety profiles consistent with previously reported studies for the combination, with no new safety signals observed.
Context and next steps
These results are described as the first positive Phase 3 readout for an individualized neoantigen therapy and for an mRNA-based cancer therapy, and the first Phase 3 study to demonstrate a clinically meaningful improvement over KEYTRUDA alone in the adjuvant melanoma setting. The trial will continue to evaluate other key secondary endpoints, including overall survival (OS). The companies plan to present the data at an upcoming international medical meeting and to engage with regulatory authorities on filings.
Source: Merck