Rondo Therapeutics, a clinical-stage biopharmaceutical company developing next-generation T-cell engaging bispecific antibodies for solid tumours, has begun dosing patients in its phase 1/1b clinical trial of RNDO-564. This first-in-class bispecific antibody targets CD28 and Nectin-4 and is being evaluated in adults with relapsed or refractory locally advanced or metastatic urothelial carcinoma and other solid tumours that express Nectin-4.

RNDO-564 has been engineered to provide tumour-directed CD28 co-stimulation, aiming to overcome key limitations associated with existing Nectin-4 antibody-drug conjugates, including durability of response and treatment-related toxicity. ADCs can lead to dose reductions, discontinuation, or relapse due to resistance, with many patients experiencing peripheral neuropathy and skin-related adverse events. Rondo’s bispecific approach is designed to deliver localised immune activation at the tumour site, promoting sustained anti-tumour activity while reducing systemic side effects.

Shelley Force Aldred, PhD, co-founder and chief executive officer of Rondo Therapeutics, said the study initiation marks a major milestone as the company advances its first co-stimulatory bispecific antibody into clinical development. Benjamin Garmezy, MD, associate director of Genitourinary Research at Sarah Cannon Research Institute and principal investigator for the trial, noted the significant unmet need among patients who relapse after ADC and immunotherapy combinations or are unable to tolerate them. He highlighted the promise of new therapeutic strategies that offer improved durability and better quality of life.

Thomas Manley, MD, chief medical officer at Rondo Therapeutics, said RNDO-564 has the potential to provide a differentiated, chemo-free option that is both effective and well tolerated.

The open-label, multicentre, first-in-human study will assess safety, tolerability, pharmacokinetics, and early anti-tumour activity of RNDO-564 as a monotherapy and in combination with pembrolizumab in patients with relapsed or refractory disease. Preclinical studies demonstrated strong Nectin-4 and T-cell receptor-dependent killing of tumour cells, inhibition of tumour growth in vivo both alone and with checkpoint inhibitors, restoration of T-cell killing after serial stimulation, and maintained efficacy in ADC-resistant cells.

Rondo Therapeutics’ broader mission is to develop bispecific antibody therapies that address critical unmet needs in solid tumour treatment by safely harnessing the immune system. Alongside RNDO-564, the company is advancing a pipeline of immune-engaging bispecifics targeting cancers such as ovarian, endometrial, and renal tumours, supported by leading global investors.