Neoadjuvant camrelizumab plus apatinib and temozolomide for resectable stage II/III acral melanoma: The CAP 03-NEO trial.

9512 Background: The CAP 03 study demonstrated significant efficacy for camrelizumab combined with apatinib and temozolomide as first-line therapy for advanced acral melanoma (AM), achieving a 64.0% objective response rate and a median progression-free survival of 18.4 months. SWOG1801 and NADINA trials suggested that neoadjuvant therapy may provide greater benefits than adjuvant therapy in melanoma. CAP 03-NEO explores the efficacy and safety of this triple-drug regimen as neoadjuvant therapy in patients (pts) with resectable stage II/III AM. Methods: This two-stage clinical trial (ClinicalTrials.gov identifier: NCT05512481) aimed to enroll 60 pts with resectable stage II/III AM aged 18–75 years. In stage 1, 30 pts received two 4-week cycles of neoadjuvant camrelizumab (200 mg intravenously every 2 weeks), apatinib (250 mg orally once daily), and temozolomide (200 mg/m² intravenously daily on days 1–5 of each cycle), followed by surgery and 15 cycles of adjuvant camrelizumab (200 mg every 3 weeks). The primary endpoint was pathological complete response (pCR). Secondary endpoints included event-free survival (EFS), overall survival, and safety. Based on pathologic non-response (pNR) rate and risk-benefit assessment, stage 2 extended enrollment to an additional 30 pts receiving the same treatment. Results: As of December 2024, all 30 pts in stage 1 were enrolled, with a median follow-up of 18.5 months. The median age was 54 years (IQR: 41–61). Of 28 pts undergoing surgery, 16 (57.1%) achieved any pathological response, including 7 (25.0%) with pCR, 5 with near pCR, and 4 with partial pathologic response (pPR). Additionally, 12 pts (42.9%) achieved major pathological response (MPR), which includes both pCR and near-pCR. Surgery was canceled for two pts due to personal reasons and new metastatic disease. Among stage II pts, 3 achieved pCR, 1 achieved pPR, and the pNR was 64%. Among stage III pts, 4 achieved pCR, 5 near PCR, and 3 pPR, with pNR of 29.4%. The median EFS has not been reached, with a 12-month EFS rate of 74.1% (95% CI: 53.1-86.7%). The most common adverse events (AEs) were increased blood bilirubin (11, 37%), decreased white blood cell count (9, 30%), and constipation (8, 27%), with no grade 4-5 AEs observed. Neoadjuvant therapy did not increase surgical complications. Conclusions: Stage 1 results of CAP 03-NEO demonstrated the potential of neoadjuvant camrelizumab, apatinib and temozolomide in pts with resectable stage II/III AM. The pNR result support advancing to stage 2 to further assess the efficacy and safety of this regimen in pts with stage III disease. Clinical trial information: NCT05512481 .