The Top Melanoma News of 2025

The past year in the melanoma space has been defined by excitement and renewed optimism for new entrants into the treatment landscape. A prevailing theme of melanoma conversations this year was the phase 2 C-144-01 trial of lifileucel (Amtagvi), which set a new benchmark for tumor-infiltrating lymphocyte (TIL) therapy and continues to demonstrate sustained, meaningful responses in patients with few remaining treatment options. Further, important regulatory developments added both momentum and caution, ensuring that emerging therapies are held to rigorous standards while still encouraging innovation.

From the promising durability of TIL therapy to novel developments at the melanoma-microbiome nexus, here are the top 5 stories that shaped the field in 2025.

Lifileucel Offers Promising Long-Term Efficacy in Advanced Melanoma

Lifileucel, a TIL therapy indicated for pretreated unresectable or metastatic melanoma, offers promising long-term efficacy for patients who have progressed on prior immune checkpoint inhibitor (ICI) therapy. During a live Community Case Forum meeting, Dr Barbara T. Ma of Weill Cornell Medicine and New York Presbyterian hospital discussed the phase 2 C-144-01 trial of lifileucel in this heavily pretreated population, which boasted an objective response rate (ORR) of 31.4% and 5-year overall survival rate of 19.7%.

A key takeaway was the durability of response, with a median duration of 36.5 months, and responses often deepening over time. The regimen requires initial hospitalization for lymphodepleting chemotherapy and the TIL infusion, with associated short-term toxicities like thrombocytopenia and febrile neutropenia occurring mostly in the first 2 weeks. Lifileucel’s performance in this trial offers hope for long-term efficacy in this patient group who otherwise have limited treatment options.

Awareness of TIL Therapy for Melanoma Is Crucial for Timely Referral

During the same live event, Dr Ma emphasized the critical need for logistical coordination and timely referral to authorized centers for lifileucel TIL therapy in patients with advanced melanoma who have progressed on prior treatment lines.

Dr Ma outlined the complex process of receiving TIL therapy, which involves surgical tumor procurement for cell manufacturing and a necessary 2-to-3-week inpatient stay for lymphodepleting chemotherapy and the TIL infusion with IL-2, managed by an experienced team to handle acute toxicities. Timely coordination is essential, as the treatment window can be narrow in patients with rapidly progressing disease.

Behind the C-144-01 Study of Lifileucel in Melanoma

In a June interview with Targeted Oncology, Dr Theresa Medina of the University of Colorado Cancer Center discussed the background of the C-144-01 study of lifileucel in advanced melanoma.

As the first global, multicenter study of TIL, the trial enabled multiple centers worldwide to provide access to this transformative one-time autologous immunotherapy for patients refractory to standard therapies such as ICIs and, when applicable, targeted therapies. The phase 2 trial demonstrated compelling efficacy, with patients treated with lifileucel achieving a notable ORR, and ultimately helped support its regulatory approval for unresectable or metastatic melanoma after PD-1 therapy.

FDA Issues CRL for RP1 in Advanced Melanoma

In July, the FDA issued a complete response letter (CRL) for Replimune's biologics license application for RP1 (vusolimogene oderparepvec), an oncolytic immunotherapy, combined with nivolumab (Opdivo) for advanced melanoma.

The FDA’s reasoning for the decision was that the pivotal IGNYTE trial lacked the characteristics of an adequate and well-controlled investigation necessary to establish effectiveness. Key issues cited included heterogeneity within the patient population and questions about the confirmatory trial's design; notably, no safety concerns were raised. Following a Type A meeting with the FDA to discuss a path forward for accelerated approval, Replimune reported that a path had not been determined.

Camu Camu Shows Safety in Patients with Melanoma and Non–Small Cell Lung Cancer

A phase 1 clinical trial revealed that the prebiotic camu camu, which contains the active compound castalagin, was safe when combined with ICIs for patients with melanoma and non–small cell lung cancer.

Results from the trial, presented at the 2025 ESMO Congress, showed promising antitumor activity with camu camu, achieving an ORR of 57% in the first-line melanoma cohort and 13% among patients with refractory melanoma. The results suggest camu camu may enhance the effectiveness of ICI by modulating the gut microbiome. Future mechanistic and clinical studies with the pure compound castalagin are planned.