Neoadjuvant anti–PD-1 prolgolimab monotherapy in resectable high-risk melanoma: Pathologic response and early event-free survival in a prospective single-arm phase II CRISTINA study.

Abstract

9579 Background: In resectable high-risk melanoma, neoadjuvant anti–PD-1 aims to exceed the ~40% MPR benchmark; while combos may deepen response, they add tox, complexity, and cost. Recently reported data for prolgolimab+nurulimab (N = 205) showed pCR 38.5%, near-CR 4.4%, motivating evaluation of prolgolimab mono as a simpler potentially non-inferior approach. Methods: MelPRO-0322 (CRISTINA; NCT06299878) is a prospective single-arm study in resectable stage IIIB–IV melanoma: 3 neoadj doses of prolgolimab followed by radiologic assessment followed by surgery (regional lymphadenectomy or M1a-equivalent metastasectomy). Central pathology used INMC criteria. Interim analysis after full enrollment and pathology assessment. Results: Pt characteristics (N = 82): Median age 61.5 y (range 23.2–87.3); median BMI 28.2 kg/m² (21.0–46.5). Females 47 (57.3%); ECOG 0/1: 56 (68.3%)/26 (31.7%). Primary melanoma: cutaneous or UPO 73 (89.0%), acral 7 (8.5%), mucosal 2 (2.4%). Stage: IIIB 12 (15.8%), IIIC 54 (71.1%), IIID 3 (3.9%), IV 7 (9.2%); stage missing 6 (7.3%). BRAF V600 mut in 43/74 (58.1%). Median neoadj tx duration 28 d (0–108). Median time from start of neoadj tx to surgery 67 d (29–176). LND/resection performed in 66/82 (80.5%). RECIST 1.1 (ITT, N = 82): ORR 23 (28.0%); CR 5 (6.1%), PR 18 (22.0%), SD 27 (32.9%), PD 24 (29.3%); not evaluable 8 (9.8%). Pathologic response (ITT, N = 82): pCR 28 (34.1%), near-pCR 7 (8.5%), MPR 35 (42.7%); pathology not available in 16 (19.5%). Among evaluable (n = 66): pCR 42.4%, MPR 53.0%. Achieving MPR correlated with better radiologic response by RECIST (p < 0.001) and lower nodal tumor burden (fewer positive nodes; p = 0.012). With a median follow-up of 11.8 mo by reverse KM (95% CI 7.5–17.4), EFS in the ITT cohort (N = 82; events = relapse/progression/death) showed 20 events with median EFS 32.2 mo (95% CI not estimable) and RMST 29.8 mo (SE 4.71). In the pathology-evaluable set (n = 66), EFS was longer in pts achieving MPR vs non-MPR/PD (log-rank p = 0.002): median EFS 19.3 mo for non-MPR/PD (n = 31; 10 events) vs not reached for MPR (n = 35; 2 events); RMST 20.3 vs 30.1 mo. In exploratory multivariable Cox models, MPR remained strongly associated with improved EFS (HR 0.043, 95% CI 0.003–0.684; p = 0.026), while higher PLT/LYM ratio (HR 1.029, 95% CI 1.006–1.052; p = 0.015) and male sex (HR 8.74, 95% CI 1.12–68.21; p = 0.039) showed associations with inferior EFS, while time from neoadj start to surgery and receipt of adjuvant therapy were not associated with EFS. Conclusions: NST prolgolimab monotherapy achieved MPR rates above the historical benchmark with encouraging early EFS. MPR—especially pCR—was strongly associated with improved EFS, with no progressions observed among pCR pts. In exploratory analyses, neither time from neoadj start to surgery nor receipt of adjuvant therapy appeared to materially affect EFS. Clinical trial information: NCT06299878 .