(UroToday.com) The 2026 American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting, held in Chicago, IL, will host the Kidney and Bladder Cancer - Posters. Dr. John D. Powderly II will present Abstract TPS4640: RNDO-564-001: A first-in-human, phase 1/1b study of RNDO-564, a costimulatory bispecific antibody for the treatment of advaned bladder cancer and other Nectin-4-positive solid tumors.
Dr. Powderly will highlight that RNDO-564 is a novel CD28 x Nectin-4 bispecific antibody engineered with high-affinity Nectin-4 binding and optimized CD28 costimulatory domains designed to maximize the therapeutic window. Given the high expression of Nectin-4 across urothelial carcinoma and several solid tumors, RNDO-564 is being developed as a potential next-generation immunotherapy strategy capable of enhancing T-cell activation while maintaining an acceptable safety profile.
The primary objectives of the study are to evaluate safety, tolerability, and establish the recommended phase 2 dose (RP2D) of intravenous RNDO-564 administered on Days 1, 8, and 15 of a 21-day cycle.
The monotherapy dose-escalation portion incorporates an accelerated titration design with four single-patient cohorts, followed by more gradual dose escalation using a Bayesian Optimal Interval (BOIN) design with backfill cohorts. Eligible patients include those with relapsed/refractory locally advanced or metastatic urothelial carcinoma, cervical cancer, head and neck cancer, esophageal cancer, gastric or gastroesophageal cancers, non-small cell lung cancer, and triple-negative breast cancer who have exhausted, declined, or are ineligible for standard therapies.
Importantly, patients previously treated with Nectin-4–directed therapies or prior MMAE exposure are eligible, as are patients with ongoing grade ≤2 peripheral neuropathy. Patients with active or prior inflammatory skin conditions are excluded.
Dr. Powderly will note that enrollment into Cohorts 1 and 2 was completed without dose-limiting toxicities, and enrollment into Cohort 3 opened in January 2026.
Safety endpoints include adverse events graded according to CTCAE v6.0. Secondary endpoints include clinical activity, pharmacokinetics, and anti-drug antibody development. Exploratory analyses will evaluate tumor Nectin-4 expression by immunohistochemistry, CD28 receptor occupancy, T-cell activation, and serum cytokine profiles.
The study also includes dose-optimization cohorts in relapsed/refractory urothelial carcinoma, with up to two 20-patient cohorts planned to further define the optimal RP2D. Separate dose-escalation and optimization cohorts evaluating RNDO-564 in combination with pembrolizumab are also planned.
RNDO-564-001 represents an important early-phase platform study evaluating a novel CD28 x Nectin-4 bispecific antibody strategy in urothelial carcinoma and other Nectin-4–positive malignancies, with ongoing enrollment aimed at defining the safety profile, preliminary antitumor activity, and optimal dosing strategy for future development.
Presented by: John D. Powderly II, MD, Medical Oncologist at Carolina BioOncology Institute in Huntersville, NC.
Written by: Julian Chavarriaga, MD, Clinical Assistant Professor, Urologic Oncologist, Department of Urology at Penn State Health @chavarriagaj on X during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026