RC48G001: A phase 2 study of disitamab vedotin in HER2-expressing previously treated advanced UC

Abstract

LBA631 Background: An estimated 60%-80% of patients (pts) with UC have HER2-expressing tumors. DV is an ADC comprising a novel anti-HER2 antibody, disitamab, and an MMAE payload. DV demonstrated promising antitumor activity and a manageable safety profile as monotherapy in Chinese pts with HER2-expressing (IHC 1+ or greater) la/mUC refractory to prior therapies. We report the primary analysis from Cohorts A and B of the global RC48G001 study assessing DV monotherapy in pts with HER2-expressing la/mUC (HER2-positive: IHC 3+, or IHC 2+/ISH-positive [Cohort A]; HER2-low: IHC 2+/ISH-negative, or IHC 1+ [Cohort B]) who progressed following systemic therapy. Method(s): RC48G001 (or C5731002) is a global, multicohort, single-arm, open-label, phase 2 study that enrolled pts with la/mUC who received 1-2 prior systemic therapies (incl. a platinum-containing regimen). HER2 expression was determined by central laboratory using the VENTANA HER2 IHC and HER2 Dual ISH DNA Probe Cocktail assays. Pts received 1.5 mg/kg DV monotherapy IV once per 2-week cycle. The primary endpoint (EP) was cORR per RECIST 1.1 by BICR. Secondary EPs included DOR, DCR, PFS (all per RECIST 1.1 by BICR), OS, and safety. A genAI tool (09/05/25; Pfizer; GPT-4o) assisted with the 1st draft; authors assume content responsibility. Result(s): At data cutoff (Sep 12, 2025), 73 pts were enrolled in Cohort A and 78 pts in Cohort B. 54.8% and 39.7% of pts had ECOG PS 0, and 68.5% and 82.1% had visceral disease in each cohort, respectively. Cohort A included 69.9% pts with IHC 3+ and 30.1% pts with IHC 2+/ISH-positive la/mUC. Cohort B included 28.2% pts with IHC 1+ and 69.2% pts with IHC 2+/ISH-negative la/mUC. Median follow-up was 11.3 months for Cohort A and 17.1 months for Cohort B. Pts received a median of 9 DV cycles in both cohorts. cORR per BICR was 54.9%, with a CR rate of 16.9%, in Cohort A, and 52.6%, with a CR rate of 18.4%, in Cohort B (Table). mPFS by BICR was 5.7 months in both cohorts. mOS was 20.0 months and 17.0 months in Cohort A and B, respectively. Grade >=3 TRAEs occurred in 62 (41.1%) pts, with fatigue (13.9%) being the most common. 16.6% of pts discontinued treatment (tx) due to AEs, most commonly peripheral sensory neuropathy (6.0%). Conclusion(s): This is the first presentation of DV monotherapy outcomes in a global population with HER2-expressing la/mUC. DV demonstrated promising antitumor activity and a manageable safety profile, consistent with results from China, supporting further evaluation. Clinical trial information: NCT04879329. [Table presented] Copyright © 2026 by American Society of Clinical Oncology