4506 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease, with substantial recurrence risk after radical cystectomy and pelvic lymph node dissection (RC + PLND) alone. SHR-A2102 is a nectin-4-targeted antibody-drug conjugate carrying topoisomerase I inhibitor payload. This phase 2/3 study (NCT06879145) evaluates the efficacy and safety of SHR-A2102 in combination with adebrelimab (an anti-PD-L1 antibody) as perioperative treatment for MIBC. Here, we report the preliminary results from the phase 2 study. Methods: In the multicenter phase 2 part, pts aged ≥18 years, ECOG PS 0-1, with pathologically and radiographically confirmed T2-4aN0M0 or T1-4aN1M0 MIBC, and scheduled for RC + PLND were enrolled. Pts received neoadjuvant treatment with 4 cycles of intravenous SHR-A2102 (8 mg/kg, day 1 Q3W) and adebrelimab (1200 mg, day 1 Q3W), followed by surgical resection and 5 additional cycles of adjuvant SHR-A2102 (8 mg/kg, day 1 Q3W) plus 13 additional cycles of adjuvant adebrelimab (1200 mg, day 1 Q3W). The primary endpoints are the recommended phase 3 dose (RP3D) and investigator-assessed pathological complete response (pCR, defined as pT0N0). Results: As of Nov 24, 2025, 37 pts were enrolled; 91.9% were male and the median age was 66 years (IQR 59-74). The ECOG PS was 0 in 24.3% of pts and 1 in 75.7%. Regarding disease stage, 29.7% were classified as T2N0, 51.4% as T3-4aN0, and 18.9% as T1-4aN1. Among 7 pts with target lesions, the neoadjuvant regimen achieved an objective response rate of 71.4% (5/7; 95% CI 29.0–96.3) and a disease control rate of 100.0% (95% CI 59.0–100.0). A total of 27 pts underwent RC + PLND, 13 (48.1%, 95% CI 28.7-68.1) achieved pCR and 16 (59.3%, 95% CI 38.8-77.6) attained pathological downstaging ( < pT2N0). Consistent pCR benefits were observed across all predefined subgroups, with creatinine clearance ＜60 mL/min showing no discernible effect on pCR rates. Of the 10 pts who refused or were ineligible for radical surgery after neoadjuvant therapy, 5 received transurethral resection of bladder tumor and 3 of whom achieved a complete clinical response (cCR, defined as T0N0M0). With the median follow-up of 4.7 months (IQR 2.1-6.6), 3 event-free survival events were reported. Grade 3 or higher adverse events occurred in 40.5% (15/37) of the pts, primarily decreased neutrophil count (16.2%) and decreased lymphocyte count (10.8%). No patient was ineligible for surgery due to adverse events. Conclusions: Perioperative treatment with SHR-A2102 plus adebrelimab showed promising efficacy and was well tolerated in pts with MIBC. This combination holds potential benefit even for pts with renal impairment, suggesting its clinical applicability may extend beyond cisplatin-eligible populations. These results support further investigation for SHR-A2102 plus adebrelimab in this population. Clinical trial information: NCT06879145 .
Ye et al. (Wed,) studied this question.