Rondo Therapeutics starts administering doses in Phase I/Ib trial for solid tumors

Rondo Therapeutics has commenced patient dosing in its Phase I/Ib trial of RNDO-564, a novel bispecific antibody targeting CD28 and Nectin-4 in advanced solid tumors. The study focuses on adults with relapsed or refractory locally advanced or metastatic urothelial carcinoma (mUC) and other Nectin-4expressing malignancies.

RNDO-564 aims to overcome the limitations seen with Nectin-4directed antibody-drug conjugates (ADCs), including treatment-related toxicities and reduced durability of response, which can lead to dose reductions or therapy discontinuation. The open-label, first-in-human, multi-center trial will evaluate the drugs pharmacokinetics, safety, tolerability, and early anti-tumor activity.

The antibody will be tested both as a single agent and in combination with pembrolizumab in patients with relapsed or refractory locally advanced or metastatic urothelial carcinoma. Preclinical studies demonstrated that RNDO-564 effectively kills Nectin-4expressing tumor cells via dual mechanismsdirect targeting of Nectin-4 and T-cell receptor-mediated cytotoxicity. The therapy also inhibited tumor growth in vivo, enhanced the effectiveness of checkpoint therapies, restored T-cell killing capacity after repeated stimulation, and retained cytotoxic activity against ADC-resistant cells.

Rondo Therapeutics co-founder and CEO, Shelley Force Aldred, highlighted that RNDO-564 is designed to maximize therapeutic potential through localized CD28 co-stimulation at the tumor site, ensuring safe and effective anti-tumor action. The trial represents a key milestone for the company as it advances its first co-stimulatory bispecific antibody into clinical testing.

Benjamin Garmezy, the principal investigator for the RNDO-564-001 trial, emphasized the ongoing need for new treatment options for patients who relapse or cannot tolerate ADC/IO combinations, noting the potential for RNDO-564 to extend disease control and improve quality of life.

Author: Chloe Ramirez