Melanoma Monthly Rewind: Key News and Expert Insights You May Have Missed in September 2025

September featured an array of updates across the melanoma landscape, including the FDA approval of a subcutaneous formulation of an immune checkpoint inhibitor, plus additional news on the development of the oncolytic virus RP1 (vusolimogene oderparepvec) and reported data from phase 2 and 3 studies.

Read on below to catch up on some of OncLive’s top coverage of melanoma news and trends for the month.

FDA Regulatory Updates

Path Toward Accelerated Approval of RP1 in Advanced Melanoma Remains Unclear After FDA Type A Meeting

Replimune and the FDA completed a Type A meeting to hold further discussions following a complete response letter (CRL) from regulatory agency for the biologics license application (BLA) seeking the approval of RP1 in combination with nivolumab (Opdivo) for the treatment of patients with advanced melanoma.1

Replimune is reviewing the FDA’s feedback, but a path toward accelerated approval of the oncolytic virus–based combination has not yet been determined.

The CRL was for the BLA seeking the approval of RP1 in combination with nivolumab for the treatment of adults with advanced melanoma who have previously received a PD-1 inhibitor–containing regimen.2,3 The CRL detailed that the phase 1/2 IGNYTE trial (NCT03767348) did not meet the threshold to be considered an adequate and well-controlled clinical investigation to produce substantial evidence supporting approval.2

FDA Approves Subcutaneous Pembrolizumab for Solid Tumors

The FDA has approved pembrolizumab and berahyaluronidase alfa-pmph (subcutaneous pembrolizumab; Keytruda Qlex) for subcutaneous injection for use in adult and pediatric (12 years and older) solid tumor indications approved for the intravenous formulation of pembrolizumab (Keytruda).4

Clinical Trial News

Lifileucel Shows Durable 5-Year Benefit in Advanced Melanoma Resistant to Immune Checkpoint Inhibitors

In an interview with OncLive, Theresa Medina, MD, discussed the final results from the phase 2 C-144-01 trial (NCT02360579) evaluating lifileucel (Amtagvi) in patients with advanced melanoma following a prior immune checkpoint inhibitor–containing regimen. Findings demonstrated that lifileucel yieldeda 5-year overall survival rate of 19.7%, and among the 31.4% of patients to achieve a response, 31.3% remained in ongoing remission at the 5-year assessment.5

Neoadjuvant Daromun Yields Improved Recurrence-Free Survival in Locally Advanced Melanoma

Neoadjuvant intralesional daromun, a combination of the fibronectin-targeting immunocytokines L19IL2 and L19TNF, followed by surgery, demonstrated significantly longer recurrence-free survival compared with upfront surgery in patients with locally advanced melanoma, according to data from the phase 3 PIVOTAL trial (NCT02938299) published in Annals of Oncology.6

Neoadjuvant Darovasertib Produces Preliminary Responses in Uveal Melanoma

Neoadjuvant treatment with the investigational PKC inhibitor darovasertib (IDE196) was effective and generally well tolerated in patients with uveal melanoma, according to preliminary data from the plaque brachytherapy cohort of the ongoing phase 2 OptimUM-09 trial (NCT05907954).7

References

1. Replimune provides update following Type A meeting with FDA. News release. Replimune. September 18, 2025. Accessed October 7, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-provides-update-following-type-meeting-fda
2. Replimune receives complete response letter from FDA for RP1 biologics license application for the treatment of advanced melanoma. News release. Replimune. July 22, 2025. Accessed October 7, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics
3. Replimune announces biologics license application acceptance and priority review for RP1 for the treatment of advanced melanoma. News release. Replimune. January 21, 2025. Accessed October 7, 2025. https://ir.replimune.com/news-releases/news-release-details/replimune-announces-biologics-license-application-acceptance-and
4. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. FDA. September 19, 2025. Accessed October 7, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-and-berahyaluronidase-alfa-pmph-subcutaneous-injection
5. Medina T, Chesney JA, Kluger HM, et al. Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study. J Clin Oncol. 2025;43(16_suppl):9515-9515. doi:10.1200/jco.2025.43.16_suppl.9515
6. Kähler KC, Hassel JC, Ziemer M, et al. Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma. Ann Oncol. 2025;36(10):1166-1177. doi:10.1016/j.annonc.2025.06.014
7. IDEAYA Biosciences announces positive interim phase 2 data for darovasertib in the neoadjuvant setting of primary uveal melanoma. News Release. IDEAYA Biosciences. September 8, 2025. Accessed October 7, 2025. https://media.ideayabio.com/2025-09-08-IDEAYA-Biosciences-Announces-Positive-Interim-Phase-2-Data-for-Darovasertib-in-the-Neoadjuvant-Setting-of-Primary-Uveal-Melanoma