Efficacy and Safety of DNV3 (a Lymphocyte‐activation Gene 3–blocking Antibody) Combined With Toripalimab and Chemotherapy in Advanced Melanoma: An Open‐label, Single‐arm Clinical Trial

ABSTRACT Despite the remarkable therapeutic advances achieved with immune checkpoint inhibitors in advanced melanoma, treatment options remain limited for patients with refractory subtypes. This study evaluated a novel combination of DNV3 (anti‐LAG‐3), toripalimab (anti‐PD‐1), and chemotherapy (nab‐paclitaxel/cisplatin) in 27 Asian patients with unresectable or metastatic melanoma (77.8% [21/27] previously treated with anti‐PD‐[L]1 and 22.2% [6/27] treatment‐naïve mucosal melanoma; subtypes: 13 mucosal, 6 acral, 5 cutaneous, and 3 of unknown primary origin). The regimen achieved an overall response rate (ORR) of 44.4%, which was further elevated to 54.5% in the subgroup of 11 patients with hepatic metastases. Notably, it also demonstrated substantial efficacy in anti‐PD‐(L)1‐resistant cases, with a 42.9% ORR and a median progression‐free survival (PFS) of 7.36 months. Among treatment‐naïve mucosal melanoma, the ORR reached 50%. At data cutoff, median overall survival remained unreached in all cohorts. Grade ≥3 treatment‐related adverse events initially occurred in 55.6% of participants; subsequent dose modification of nab‐paclitaxel (from 260 mg/m 2 to 200 mg/m 2 ) improved tolerability, reducing the incidence of grade ≥3 events to 22.2%. Immune‐related toxicities (grade 3–4, 22.2%) were clinically manageable. Therefore, the combination of LAG‐3/PD‐1 blockade and chemotherapy demonstrated promising efficacy, notably in treatment‐naïve mucosal melanoma with liver metastases. (Chinese Clinical Trial Registry number, ChiCTR2400079543)