Neoadjuvant camrelizumab plus apatinib and temozolomide for resectable stage III acral melanoma: Updated CAP 03-NEO trial results and external control comparison.

Abstract

9571 Background: 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 camrelizumab combined with apatinib and temozolomide triple-drug regimen as neoadjuvant therapy in patients (pts) with resectable stage II/III acral melanoma (AM). Methods: This two-stage trial (NCT05512481) aimed to enroll 60 pts with resectable stage II/III AM. Pts received two 4-week cycles of neoadjuvant camrelizumab (200 mg IV Q2W), apatinib (250 mg orally QD), and temozolomide (200 mg/m² IV daily D1–5), followed by surgery and 15 cycles of adjuvant camrelizumab (200 mg Q3W). A total of 30 pts were assessed in stage 1, demonstrating stage III AM benefiting more from neoadjuvant therapy (ASCO 2025, abstract 9512). Therefore, stage 2 exclusively enrolled stage III pts. Endpoints included pathological response, EFS, RFS and DMFS. To further evaluate the neoadjuvant benefit, an external contemporary cohort of stage III AM pts treated with upfront surgery and adjuvant PD-1 inhibitor alone was retrospectively collected for comparison. Propensity score matching (PSM 1:1 nearest neighbor method) and inverse probability of treatment weighting (IPTW) were used to minimize bias. Kaplan-Meier method and Cox regression were performed for survival analysis. Stage 2 results and this post-hoc comparison are reported here. Results: As of Jan. 26, 2026, thirty-one pts in stage 2 were enrolled, with a median follow-up of 13 months. The median age was 60 years (IQR: 49–68). Of 28 pts undergoing surgery, 18 (64.3%) achieved any pathological response, including 10 with major pathological response (7 with pCR, 3 with near pCR), and 8 with pPR. Surgery was canceled for 2 pts due to progressive disease. Neoadjuvant therapy was still ongoing for one patient. The 12-month rates of EFS, RFS and DMFS were 74.4%, 80.3% and 84.0%, respectively. All median values were not reached. As compared to external control cohort (adjuvant treatment alone), both unadjusted and adjusted analyses showed that pts treated with additional neoadjuvant therapy achieved significantly better EFS, RFS and DMFS (Table 1, all p values <0.05). The safety profile between stage 1 and stage 2 were similar and no new safety signal was identified. Conclusions: Stage 2 results and external control comparison of CAP 03-NEO further confirmed the significant benefit of neoadjuvant camrelizumab, apatinib and temozolomide in pts with resectable stage III AM. Clinical trial information: NCT05512481 . HR and 95% CI for EFS, RFS, and DMFS (sample size of stage 2 vs. external control). Survival Unadjusted (31 vs. 50) PSM 1:1 (30 vs. 30) IPTW (31 vs. 50) EFS 0.309 (0.129-0.743) 0.246 (0.078-0.778) 0.317 (0.124-0.810) RFS 0.244 (0.086-0.694) 0.241 (0.071-0.812) 0.242 (0.081-0.728) DMFS 0.286 (0.099-0.822) 0.203 (0.051-0.807) 0.290 (0.094-0.893)