Dr Buchbinder on the Potential Role for RP1 Plus Nivolumab in Melanoma After PD-1 Progression

“A lot of patients are undergoing TIL therapy now when they've progressed after immunotherapy. [However,] having something like an effective injection therapy, in combination with nivolumab, that we could use in this space would give us another option, particularly for those patients [who perhaps] can't [receive] TIL therapy or have even [progressed on prior] TIL therapy.

Elizabeth Buchbinder, MD, assistant professor, Medicine, Harvard Medical School, senior physician, Medical Oncology, Dana-Farber Cancer Institute, discusses the potential implications of the FDA's decision to grant breakthrough therapy designation to RP1 (vusolimogene oderparepvec) plus nivolumab (Opdivo) for the treatment of adult patients with advanced melanoma.

In November 2024, a biologics license application (BLA) was submitted to the FDA for accelerated approval of RP1 (vusolimogene oderparepvec) in combination with nivolumab (Opdivo) for the treatment of adult patients with advanced melanoma who have previously received a regimen containing a PD-1 inhibitor. This combination concurrently received breakthrough therapy designation from the FDA for the same indication. Both the BLA submission and breakthrough designation are supported by data from the anti-PD-1–progressed melanoma cohort (n = 156) of the phase 1/2 IGNYTE trial (NCT03767348).

After a median follow-up of 15.4 months, the overall response rate (ORR) in this cohort was 32.7%, including complete response (CR) and partial response (PR) rates of 14.7% and 17.9%, respectively. Among patients who had previously received anti–PD-1 monotherapy (n = 82), the ORR was 37.8%, with CR and PR rates of 22.0% and 15.9%, respectively. In those previously treated with both PD-1 and CTLA-4 inhibitors (n = 74), the ORR was 27.0%, with CR and PR rates of 6.8% and 20.3%, respectively.

Based on these data, the confirmatory phase 3 IGNYTE-3 trial (NCT06264180) is currently enrolling patients with advanced melanoma who have progressed on PD-1 and CTLA-4 therapy or are ineligible for CTLA-4 therapy. The primary endpoint of this trial is overall survival (OS), with secondary endpoints including progression-free survival (PFS) and ORR.

The current treatment landscape for advanced melanoma is evolving with the use of targeted therapies and tumor-infiltrating lymphocyte (TIL) therapy, both of which are becoming more prevalent, particularly for patients who have progressed after immunotherapy, Buchbinder says. However, the introduction of a combination like RP1 plus nivolumab offers a new and valuable option, she states. This combination could be particularly beneficial for patients who are ineligible for TIL therapy, have progressed on TIL therapy, or lack viable targeted therapy options, Buchbinder says. Additionally, patients who are not candidates for other clinical trials may find this combination to be an effective alternative, she notes. The availability of this option provides an important opportunity to expand treatment choices for advanced melanoma, potentially leading to improved outcomes for patients with limited options, Buchbinder concludes.