Intismeran autogene plus pembrolizumab improved recurrence-free survival and distant metastasis-free survival compared with pembrolizumab alone as adjuvant therapy in patients with completely resected stage IIB to IV cutaneous melanoma, according to a press release from Merck and Moderna. The findings were from the phase 3 INTerpath-001 trial, which evaluated an individualized mRNA-based neoantigen therapy in combination with pembrolizumab.
The prespecified interim analysis showed statistically significant improvements with combination therapy for both recurrence-free survival (RFS), the primary end point, and distant metastasis-free survival (DMFS), a key secondary end point. Eligible patients had completely resected stage IIB, IIC, III, or IV cutaneous melanoma and had not received prior systemic therapy. Follow-up is ongoing for other secondary outcomes, including overall survival.
The randomized, double-blind, placebo- and active-comparator-controlled trial enrolled 1,137 patients. Following complete surgical resection, patients were randomly assigned 2:1 to intismeran plus pembrolizumab or pembrolizumab alone. Intismeran was administered at 1 mg every 3 weeks for up to nine doses, and pembrolizumab was administered at 400 mg every 6 weeks for up to 9 cycles. Treatment could continue for approximately 1 year unless disease recurrence or unacceptable toxicity occurred sooner.
Intismeran is an investigational individualized neoantigen therapy created using tumor-specific information from each patient. Synthetic messenger RNA encodes as many as 34 neoantigens based on the tumor’s mutations. The resulting neoantigens are intended to stimulate T-cell responses directed against cancer cells.
No new safety signals emerged in INTerpath-001. Safety findings for the combination were consistent with previous studies of intismeran and pembrolizumab. Merck and Moderna said the findings will be presented at an international medical meeting and shared with regulatory authorities.
Earlier clinical evidence for the combination came from the phase 2b KEYNOTE-942/mRNA-4157-P201 trial in adjuvant melanoma.
Source: Moderna