Dr Sonpavde on the Ongoing Investigation of V940 Plus Pembrolizumab in High-Risk MIBC

"V940 is a very exciting molecule, because this has already shown improved outcomes in a randomized phase 2 trial in melanoma. As bladder [cancer is] a high mutation burden cancer, customizing [the treatment approach] based on the neoantigens specific for the tumor makes a lot of sense."

Guru P. Sonpavde, MD, medical director for Genitourinary (GU) Oncology, assistant director of the Clinical Research Unit, and the Christopher K. Glanz Chair for Bladder Cancer Research at AdventHealth Cancer Institute, discusses the ongoing investigation of the novel individualized neoantigen therapy V940 (mRNA-4157) plus pembrolizumab (Keytruda) as adjuvant treatment for patients with resected high-risk muscle-invasive bladder cancer (MIBC).

Sonpavde begins by explaining that V940 is a novel individualized neoantigen therapy tailored to each patient’s unique tumor-specific mutational profile. This therapy uses neoantigens derived from cancer-specific mutations, which are identified by the immune system as foreign, triggering a potent T-cell response, he says. The process involves comprehensive analysis of the patient’s tumor through whole exome sequencing, RNA sequencing, HLA typing, and peripheral blood sequencing to identify tumor-specific neoantigens, Sonpavde details.

V940 has previously shown antitumor activity among patients with melanoma in therandomized phase 2 KEYNOTE-942 trial (NCT03897881), leading to the initiation of a phase 3 trial in this tumor type, he notes. Given the high mutational burden of bladder cancer, this personalized neoantigen therapy is a logical extension for exploring its potential in this setting, Sonpavde states.

The phase 2 INTerpath-005 study (NCT06305767) is a multicenter, open-label, randomized, double-blind trial evaluating the combination of pembrolizumab and V940 in patients with resected high-risk MIBC. Patients will be randomly assigned 1:1 to receive either adjuvant pembrolizumab at 400 mg intravenously every 6 weeks for 9 cycles plus 1 mg of V940 intramuscularly every 3 weeks for 9 doses vs pembrolizumab plus placebo. An additional cohort is being explored in the neoadjuvant setting, combining pembrolizumab with V940 in cisplatin-ineligible patients, he adds. This combination strategy is exciting, as it combines 2 potent therapies that have demonstrated efficacy in treating patients with urothelial carcinoma, Sonpavde concludes.