First-Line Toripalimab Demonstrates Progression-Free Survival Benefit in Advanced Melanoma
Clinical Summary:
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Design/Population: This multicenter, open-label, phase 3 MELATORCH trial compared first-line toripalimab with dacarbazine in treatment-naïve patients with stage III or IV melanoma, including a majority with acral subtype disease.
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Key Outcomes: Toripalimab significantly prolonged progression-free survival compared with dacarbazine and demonstrated consistent benefit across predefined subgroups, including patients with acral melanoma. Objective response and duration of response favored toripalimab, with a manageable safety profile.
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Clinical Relevance: These findings support toripalimab as an effective first-line treatment option for advanced melanoma and provide prospective evidence supporting PD-1 inhibition in patients with acral melanoma.
Results from the phase 3 MELATORCH trial demonstrated that first-line toripalimab significantly improved progression-free survival (PFS) compared with dacarbazine in patients with advanced melanoma, supporting PD-1 inhibition as an effective treatment option for patients with acral melanoma.
“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 treatment-naïve stage III or IV melanoma were randomized 1:1 to receive either 240 mg of toripalimab every 2 weeks for up to 2 years (n = 127) or 1,000 mg/m² of dacarbazine every 3 weeks (n = 128) until disease progression or unacceptable toxicity. Patients assigned to dacarbazine were permitted to cross over to toripalimab following radiographic disease progression. Among the enrolled population, 160 patients had acral melanoma. The primary end point was PFS. 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% compared with dacarbazine (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; P = .02). The PFS benefit was consistent across most predefined subgroups, including patients with acral melanoma.
Objective response and duration of response also favored toripalimab. Median duration of response was 13.8 months with toripalimab compared with 6.9 months with dacarbazine.
Grade ≥3 treatment-related adverse events occurred in 28.3% of patients receiving toripalimab. The most common treatment-related adverse events occurring in ≥3% of patients included increased lipase (8.7%), anemia (3.9%), increased γ-glutamyl transferase (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
