Novel Bispecific ADC Earns FDA Fast Track Status in Urothelial Cancer

The FDA has granted fast track designation to AVZO-103, an investigational Nectin4/TROP2 bispecific antibody drug conjugate (ADC), as a treatment for adults with locally advanced or metastatic urothelial cancer following prior receipt of enfortumab vedotin-ejfv (Padcev), according to a press release from the developer, Avenzo Therapeutics.¹

According to the developers, there are no currently approved ADCs for patients who previously received enfortumab vedotin. Investigators are currently evaluating the safety, tolerability, and preliminary activity of AVZO-103 administered alone or in combination with other agents among patients with advanced solid tumors in the phase 1/2 AVZO-103-1001 trial (NCT07193511).

“Receiving fast track designation for AVZO-103 highlights the significant need for treatment options for patients with urothelial cancer who have progressed on enfortumab vedotin,” Mohammad Hirmand, MD, co-founder and chief medical officer at Avenzo Therapeutics, stated in the press release.¹ “We believe AVZO-103 has the potential to become a promising treatment option for patients and we are committed to rapidly advancing its clinical development.”

In phase 1 of the first-in-human study, investigators will determine the safety, tolerability, maximum tolerated dose, and preliminary recommended phase 2 dose of AVZO-103 monotherapy as part of a dose-escalation design.² Phase 2 will include a dose-expansion portion that will evaluate the antitumor activity of the novel agent alone or with other therapies.

The trial’s primary end points include the occurrence of dose-limiting toxicities, the maximum tolerated dose and/or recommended phase 2 dose, and the incidence of treatment-emergent adverse effects (TEAEs) and lab abnormalities in phase 1. The primary end point of the phase 2 portion of the trial is objective response rate per RECIST v1.1 criteria. Secondary end points include duration of response, disease control rate, progression-free survival, overall survival, and pharmacokinetic parameters.

Patients 18 years and older with histologically or cytologically confirmed locally advanced or metastatic malignancies, including locally advanced or metastatic urothelial cancer and other solid tumors, are eligible for enrollment on the trial. Other eligibility criteria include having an ECOG performance status of 0 or 1, a life expectancy of more than 3 months, measurable disease per RECIST v1.1 guidelines, and willingness to provide molecular test report results to confirm eligibility as well as archival tumor samples.

Those with active central nervous system metastases, prior Stevens-Johnson syndrome or toxic epidermal necrolysis, a history of drug-related interstitial lung disease, or a history of any serious cardiovascular condition are unable to enroll on the study. Patients also cannot enroll if they have an infection requiring intravenous antibiotics, antifungals, or antivirals within 2 weeks of beginning study treatment or prior allogenic stem cell or solid organ transplant. Patients with asymptomatic and treated brain metastases that are radiologically stable for a minimum of 4 weeks before beginning study therapy are eligible for enrollment.

In September 2025, developers announced the initiation of the phase 1/2 trial assessing AVZO-103 among patients with advanced solid tumors.³

“Nectin4 and TROP2 are highly co-expressed in multiple solid tumors, including urothelial cancer, and contribute to tumor growth and progression. By targeting both Nectin4 and TROP2, AVZO-103 has the potential to overcome tumor heterogeneity, while also delivering a potent cytotoxic payload that could help overcome resistance to prior therapies,” Benjamin Garmezy, MD, associate director of genitourinary research and executive cochair of the Genitourinary Cancer Research Executive Committee at Sarah Cannon Research Institute (SCRI) and medical oncologist at SCRI Oncology Partners specializing in genitourinary cancers, stated in a press release at the time of the trial’s initiation.³

References

1. Avenzo Therapeutics granted fast track designation for AVZO-103, a potential best-in-class Nectin4/TROP2 bispecific antibody-drug conjugate, for the treatment of patients with urothelial cancer previously treated with enfortumab vedotin. News release. Avenzo Therapeutics. November 24, 2025. Accessed November 24, 2025. https://tinyurl.com/2td79eur
2. Study of AVZO-103 as a single agent and in combination therapy in patients with locally advanced or metastatic urothelial cancer or other solid tumors (AVZO-103-1001). ClinicalTrials.gov. Updated November 12, 2025. Accessed November 24, 2025. https://tinyurl.com/y5ux2dht
3. Avenzo Therapeutics initiates phase 1/2 clinical study of AVZO-103, a potential best-in-class Nectin4/TROP2 bispecific antibody-drug conjugate. News release. Avenzo Therapeutics. September 29, 2025. Accessed November 24, 2025. https://tinyurl.com/5a4a6pnh