FDA Advisory Committee Backs RP1 for Advanced Melanoma

An FDA advisory committee voted 10-3 on July 30 that efficacy results from the IGNYTE study are evaluable and clinically meaningful for RP1 (vusolimogene oderparepvec) in combination with Opdivo (nivolumab) in adults with advanced melanoma that has progressed after an anti-PD-1-containing regimen.

The vote by the Cellular, Tissue, and Gene Therapies Advisory Committee is not an approval. Committee recommendations are nonbinding, the FDA's target action date is Aug. 2 and RP1 is not available outside of a clinical trial.

What the committee weighed

RP1 is an oncolytic immunotherapy based on a modified herpes simplex virus. It is injected directly into a tumor and is designed to prompt an immune response against tumors elsewhere in the body.

The application has gone through three review cycles and two complete response letters, issued in July 2025 and April 2026. The FDA's central objection has been the study design. IGNYTE was single-arm, meaning all participants received the combination and there was no comparison group. Agency reviewers questioned whether that design can separate the contribution of RP1 from that of Opdivo.

In IGNYTE, the objective response rate was 33.6%, with a median duration of response of 24.8 months and median overall survival of 32.9 months. Treatment-related side effects of grade 3 or higher occurred in 31.4% of participants.

Committee members who voted no cited standards of evidence rather than the drug's potential value.

Where TIL therapy entered the discussion

Amtagvi (lifileucel), a tumor-infiltrating lymphocyte therapy, is the only FDA-approved treatment for melanoma that has progressed after anti-PD-1 therapy. It came up repeatedly during the meeting.

Replimune's briefing materials cited Amtagvi's 2024 accelerated approval, which was also based on a single-arm trial and showed a response rate of 31.5%, as precedent for approving RP1 on similar evidence. According to those same briefing materials, nearly all participants in the Amtagvi trial experienced grade 4 treatment-related events. The company stated that a need remains for options that are both safe and effective.

A patient's account of TIL therapy

TIL therapy involves surgery to collect immune cells from a tumor, several weeks while those cells are grown in a lab, chemotherapy to prepare the body, the cell infusion and then interleukin-2, or IL-2.

Dr. James Smithy, a medical oncologist at Memorial Sloan Kettering Cancer Center, has said TIL is a one-time infusion rather than a series of cycles, so most side effects occur within a predictable one-month window. He has recommended that patients learn about TIL as a potential next step while still on first-line immunotherapy, before a decision becomes urgent.

Michael Goldman, who has stage 4 melanoma and received TIL therapy, described the IL-2 phase on CURE Connections as the most difficult part. Chills began about 30 minutes after each dose, he said.

"Once I got that first chill, I knew it was coming," Goldman said. The rigors built into 20 to 30 minutes of shaking and fever before subsiding.

That pattern held for four doses. After the fifth, Goldman was transferred to the intensive care unit. Smithy said Goldman most likely had a small seizure, and that the extent of his brain involvement placed him at higher risk. Seizure medication worked quickly, and Goldman left the ICU within about 24 hours. His brain disease has remained controlled since, Smithy said.

Goldman described the rest of the process as smooth.

"It's been a home run," he said. "Eleven days of your life to sacrifice in the hospital, for leaving the hospital and not having to take anything and have your body actively fighting successfully against your cancer, is a win."

"With TIL, I was given a new immune system, a new cancer-fighting immune system," Goldman said.

His advice to patients who are newly diagnosed centers on time. "Every day you can prolong your life is an extra day of a chance that something else comes out that can save your life," he said.

"I'm a big fan of TIL," he said, "and I think it's a good treatment that more people should be aware of."

"Eleven days of your life to sacrifice in the hospital, for leaving the hospital and not having to take anything and have your body actively fighting successfully against your cancer, is a win."
— Michael Goldman, CURE Connections

What happens next

The FDA is expected to act by Aug. 2. The confirmatory phase 3 IGNYTE-3 trial is ongoing, with overall survival data expected in 2030.

Patients whose melanoma has progressed on anti-PD-1 therapy may want to ask their oncology team whether they are candidates for TIL therapy now, whether waiting would change that and whether any clinical trials are open to them.

References

1. "Cellular, Tissue, and Gene Therapies Advisory Committee July 30, 2026 Meeting Announcement." U.S. Food and Drug Administration, July 30, 2026.
2. "BLA 125827 Vusolimogene Oderparepvec (RP1): FDA Briefing Document." U.S. Food and Drug Administration, July 30, 2026.
3. "BLA 125827 Vusolimogene Oderparepvec (RP1): Advisory Committee Briefing Materials." Replimune, Inc., July 30, 2026.
4. "Replimune Announces Favorable Outcome of FDA's Cellular, Tissue, and Gene Therapies Advisory Committee Meeting for RP1 in Advanced Melanoma" News Release. Replimune Group, Inc., July 30, 2026.
5. "Replimune Announces FDA Acceptance of RP1 Biologics License Application Resubmission for Advanced Melanoma" News Release. Replimune Group, Inc., June 26, 2026.
6. "Navigating the IL-2 Experience." CURE Connections, CURE, May 8, 2026.
7. "Looking Ahead and Advice for Newly Diagnosed Patients." CURE Connections, CURE, May 29, 2026.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.