First-Line Toripalimab Improves PFS in Advanced Melanoma Predominantly of Acral Subtype
Key Clinical Takeaways:
- Design/Population: This multicenter, open-label phase 3 trial randomized 256 patients with treatment-naïve stage III or IV melanoma, including a majority with acral subtype disease, to toripalimab or dacarbazine. Progression-free survival was assessed by blinded independent central review.
- Key Outcomes: Toripalimab significantly reduced the risk of disease progression or death compared with dacarbazine and demonstrated consistent benefit across predefined subgroups, including acral melanoma. Objective response rate and duration of response also favored toripalimab, with manageable toxicity.
- Clinical Relevance: These findings establish toripalimab as an effective first-line treatment option for advanced melanoma, particularly in patients with acral subtype disease, an area of prior unmet need. The results support PD-1 inhibition as a viable strategy in this distinct melanoma population.
Results from the phase 3 MELATORCH trial demonstrated that first-line toripalimab significantly improved progression-free survival (PFS) compared to dacarbazine among patients with advanced melanoma, including those with predominantly acral subtype disease.
“Programmed cell death 1 (PD-1) inhibitors have been the standard first-line treatment for advanced melanoma,” stated Xinan Sheng, MD, Peking University Cancer Hospital and Institute, Beijing, China, and coauthors. “However, their clinical benefit in advanced melanoma predominantly of acral subtype remains unclear.”
In this multicenter, open-label trial, 256 patients with stage III or IV melanoma who received no prior systemic therapy for advanced disease were randomized 1:1 to receive 240 mg of toripalimab (n = 127) once every 2 weeks for up to 2 years or 1000 mg/m2 of dacarbazine (n = 128) once 3 weeks until disease progression or unacceptable toxicity. Patients in the dacarbazine arm were permitted to cross over to toripalimab after radiographic progression. Of the enrolled patients, 160 had acral subtype melanoma. The primary end point was PFS, and key secondary end points included objective response rate (ORR), duration of response, and safety.
At a median follow-up of 11.8 months, toripalimab reduced the risk of disease progression or death by 29.2% (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; P = .02). PFS benefit was observed across most subgroups, including those with acral subtype. Median ORR was 11 months in the toripalimab arm and 8.6% in the dacarbazine arm, and median duration of response was 13.8 months and 6.9 months, respectively.
Grade ≥3 treatment-related adverse events were reported in 28.3% of patients in the toripalimab arm. The most frequently reported events occurring in ≥ 3% of patients included lipase increase (8.7%), anemia (3.9%), γ-glutamyl transferase increase (3.1%), hyponatremia (3.1%), and increased blood triglycerides (3.1%).
“This phase 3 randomized clinical trial found that as a first-line treatment for advanced melanoma predominantly of acral subtype, toripalimab showed a significant PFS benefit over dacarbazine and an acceptable safety profile,” concluded Dr Sheng et al.
Source:
Sheng X, Huang G, Fang M, et al. Toripalimab vs dacarbazine as first-line therapy for advanced melanoma of acral subtype. JAMA Oncol. Published online: January 2, 2026. doi:10.1001/jamaoncol.2025.5751
