- source： CentryMed
- author： CentryMed
-
2025.06.26
Shimai Pharma and Professor Yu Chen's team from Fujian Cancer Hospital presented a poster titled "Investigator-Initiated Study on DNV3 (LAG-3 Monoclonal Antibody), Toripalimab, and Chemotherapy Combination Therapy for Advanced Melanoma" at the American Society of Clinical Oncology (ASCO 2025) Annual Meeting.
Building upon DNV3's demonstrated potential to overcome PD-1 resistance in prior melanoma studies, Shimai Pharma initiated this investigator-led trial exploring the addition of low-dose chemotherapy during initial treatment cycles. The chemotherapy regimen induces immunogenic cell death in tumor cells, thereby optimizing the immune microenvironment and enhancing therapeutic efficacy.
Safety and Efficacy Analysis of DNV3, Toripalimab, and Chemotherapy in Advanced Melanoma: An Open-Label, Investigator-Initiated Study
A total of 27 patients were enrolled, with 77.8% (21/27) having prior anti-PD-(L)1 therapy. Melanoma subtypes included:
Acral: 6 cases
Mucosal: 13 cases (including 6 treatment-na?ve)
Cutaneous: 5 cases
Unknown primary: 3 cases
Safety:
At DNV3 3 mg/kg + Toripalimab 240mg combined with low-dose nab-paclitaxel (220mg/m2), no new safety signals were observed. Primary treatment-related adverse events included anemia, thrombocytopenia, leukopenia, and elevated liver enzymes.
Efficacy:
Among all 27 patients:
10 patients (including 6 with liver metastases) achieved objective responses
Overall ORR: 37%
Subtype-specific ORR:
Mucosal: 38.5%
Cutaneous: 80%
Acral: 16.7%
Median Duration of Response (DOR), Progression-Free Survival (PFS), and Overall Survival (OS) were not reached at data cutoff.
This study provides preliminary evidence for the tolerability and clinical potential of DNV3 + Toripalimab + chemotherapy in advanced melanoma, particularly for mucosal subtypes, liver metastasis patients, and PD-(L)1-treated populations. Based on these findings, a multicenter registration study of this combination is currently underway in China.
About DNV3
LAG-3 antibody DNV3 is Shimai Pharma's first-in-class oncology therapeutic developed from its proprietary ultra-large IgM antibody library. As the most promising immune checkpoint inhibitor target beyond PD-1/PD-L1, preclinical and clinical data demonstrate its exceptional potential to reverse PD-1/PD-L1 resistance.
Mechanism:
By blocking LAG-3 (on T-cells) binding to MHC-II (on tumor cells), DNV3:
Reverses T-cell exhaustion and negative regulation
Abrogates tumor immune escape mechanisms
Suppresses regulatory T-cell (Treg) function
Restores T-cell cytotoxic activity to inhibit tumor growth
Advantages:
High yield (8.1g/L)
Streamlined manufacturing processes
Favorable safety profile
Potent anti-tumor effects
Specifically overcomes tumor microenvironment immunosuppression
Addresses existing drug resistance
Significant market potential