Rondo Therapeutics Initiates First-in-Human Trial of RNDO-564, Novel Bispecific Antibody for Advanced Solid Tumors
Key Insights
Rondo Therapeutics (search) has dosed the first patient in a Phase 1/1b trial of RNDO-564, a first-in-class CD28 (search) x Nectin-4 (search) bispecific antibody designed to overcome limitations of existing ADC therapies.
The novel therapeutic targets relapsed or refractory metastatic urothelial carcinoma (search) and other Nectin-4 (search)-positive solid tumors through localized immune co-stimulation at tumor sites.
RNDO-564 aims to address significant unmet medical needs for patients who relapse on ADC/IO combinations or cannot tolerate these regimens due to adverse events.
Rondo Therapeutics (search) has achieved a significant milestone by dosing the first patient in its Phase 1/1b clinical trial of RNDO-564, a first-in-class bispecific antibody targeting CD28 (search) and Nectin-4 (search) for the treatment of advanced solid tumors. The achievement marks the company's transition to clinical-stage operations and represents a novel approach to addressing limitations of current Nectin-4-targeting therapies.
Addressing ADC Limitations Through Immune Co-stimulation
RNDO-564 represents a first-in-class therapeutic modality designed to overcome significant limitations of Nectin-4 (search)-targeting antibody-drug conjugates (ADCs). Current ADC therapies face challenges with durability of response and treatment-related toxicities that can lead to dose reductions or discontinuation. Many patients who initially respond to ADC/IO regimens relapse due to resistance or are unable to continue treatment because of adverse events including peripheral neuropathy and skin toxicities.
"We engineered RNDO-564 to deliver the widest therapeutic window through localized CD28 (search) co-stimulation at the tumor site for safe and effective anti-tumor activity," said Shelley Force Aldred, Ph.D., Co-Founder and Chief Executive Officer of Rondo Therapeutics (search).
By engaging Nectin-4 (search) on tumor cells and CD28 (search) on T cells, RNDO-564 is designed to provide localized immune co-stimulation that drives robust and sustained anti-tumor activity while minimizing peripheral toxicity.
Clinical Trial Design and Patient Population
The open-label, multicenter, first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of RNDO-564 both as a monotherapy and in combination with pembrolizumab in adults with relapsed or refractory locally advanced or metastatic urothelial carcinoma (search) (mUC) and other solid tumors associated with Nectin-4 (search) expression.
Benjamin Garmezy, M.D., Associate Director of Genitourinary Research at Sarah Cannon Research Institute (search) (SCRI) and principal investigator for the trial, emphasized the clinical need: "With the growing use of ADC/IO combinations, there remains a significant unmet need for patients whose disease relapses or who cannot tolerate these regimens. There is promise in developing new treatment options that can extend disease control and improve quality of life for these patients."
Preclinical Evidence Supporting Clinical Development
Preclinical data demonstrate RNDO-564's therapeutic potential across multiple parameters. The bispecific antibody elicited robust Nectin-4 (search) and T-cell receptor-dependent mediated killing of Nectin-4-expressing tumor cells and inhibited tumors in vivo as monotherapy and in combination with checkpoint therapy. Notably, RNDO-564 restored tumor cell killing function of serially stimulated T cells in vitro and maintained cytotoxicity in ADC-resistant cells.
"We believe RNDO-564 has the potential to fill this gap by offering a differentiated, chemo-free therapeutic option that is both durable and well tolerated," said Thomas Manley, M.D., Chief Medical Officer at Rondo Therapeutics (search).
Company Pipeline and Strategic Focus
Rondo Therapeutics (search) is developing a new class of bispecific antibodies designed to harness the immune system to target and eliminate tumors with enhanced safety. Beyond RNDO-564, the company's pipeline includes immune-engaging bispecifics for a range of solid tumors, including ovarian, endometrial, and renal cancers. The company is supported by Canaan Partners, Red Tree Venture Capital, Johnson & Johnson, SV Health Investors, and Novo Holdings.