Dr Sullivan on RP1 Plus Nivolumab in Anti–PD-1–Refractory Melanoma

“The fact that [activity is observed in non-injected lesions] can happen suggests that [RP1 has] the ability to educate the immune system in such a way that it can help [lead] to [the] attack of tumors that [were not] injected and [are not] nearby, and that’s pretty interesting.”

Ryan Sullivan, MD, director, Center for Melanoma, Massachusetts General Hospital, discusses findings from the phase 2 IGNYTE trial (NCT03767348) evaluating RP1 in combination with nivolumab (Opdivo) in patients with advanced melanoma who progressed on prior anti–PD-1 therapy.

RP1 is an oncolytic herpes simplex virus engineered to selectively infect and lyse tumor cells, releasing tumor-associated antigens and stimulating an immune response. This approach aims to activate immune cells capable of recognizing both injected and non-injected tumors. When combined with nivolumab, RP1 could enhance systemic immune activation, potentially overcoming resistance to immune checkpoint inhibition.

Sullivan notes that the trial enrolled patients with anti–PD-1–refractory melanoma, including a subset with primary resistance, defined as those who derived no initial benefit from checkpoint inhibition. Results demonstrated an objective response rate (ORR) of 33.6% by modified RECIST 1.1 criteria and 32.9% by standard RECIST 1.1 criteria per independent central review.

Sullivan highlights that responses were observed in both injected and distant, non-injected lesions, suggesting that RP1 induces immune activation beyond local tumor lysis. Although some responses may result from regional immune stimulation, similar to talimogene laherparepvec (T-VEC), an FDA-approved oncolytic virus,the IGNYTE data suggest that RP1 has the potential for broader systemic tumor control.

Given the observed clinical activity in this heavily pretreated, checkpoint inhibitor–resistant population, Sullivan concludes that further randomized trials are warranted to confirm RP1’s efficacy and define its role in the second-line setting for melanoma. If validated, RP1 in combination with nivolumab could represent a promising therapeutic option for patients with limited treatment alternatives following progression on a PD-1 inhibitor.