FDA Grants Fast Track Designation to DB-1303 for HER2+ Endometrial Cancer

The FDA has granted fast track designation (FTD) to DB-1303 for the treatment of patients with HER2-overexpressing advanced, recurrent, or metastatic endometrial cancer following progression on or after standard-of-care treatment, according to a press release from Duality Biologics.

Investigators are assessing DB-1303 in an ongoing phase 1/2a trial (NCT05150691) among patients with advanced or metastatic HER2-positive or HER2-low solid tumors. Phase 1 of the study included an accelerated titration at the first dose level to determine the maximum-tolerated dose and recommend phase 2 dose of DB-1303. Part 2 is the dose expansion phase of the study that was designed to confirm the efficacy, safety, and tolerability of the agent.

“The FDA's decision to grant FTD underscores the potential for DB-1303 to address the unmet medical need and potentially serve as a new therapeutic option for patients with advanced, recurrent, or metastatic endometrial carcinoma,” John Zhu, PhD, MBA, founder and chief executive officer at Duality Biologics, said in the press release.

The novel antibody-drug conjugate DB-1303 was designed to have potent anti-tumor activity in both HER2-positive and HER2-low tumors. The agent yields a bystander killing effect, high plasma stability, low free payload in circulation, and wide therapeutic index. The agent contains an anti-HER2 monoclonal antibody, an enzymatically cleavable peptide linker, and proprietary topoisomerase I inhibitor P1003.

Investigators of the multicenter, non-randomized, open-label study administered DB-1303 intravenously on day 1 of each cycle once every 3 weeks at various dose levels in patients with HER2-positive advanced solid tumors.

Primary end points for the phase 2a portion of the trial included treatment-emergent adverse effects (TEAEs), serious AEs, and objective response rate as assessed per RECIST v1.1 criteria. Secondary end points included the pharmacokinetics of DB-1303, disease control rate, duration of response, time to response, and percent change in target lesions based on RECIST v1.1 criteria.

Patients 18 years and older with a pathologically documented HER2-positive or HER2-expressing advanced or unresectable, recurrent, or metastatic malignant tumors were eligible to enroll on the trial. Additional inclusion criteria included having at least 1 measurable lesion per RECIST v1.1 criteria, providing signed informed consent, having an ECOG performance status of 0 or 1, adequate organ function, and a life expectancy of at least 3 months.

Patients with a history of symptomatic congestive heart failure or a history of myocardial infarction or unstable angina within 6 months before the first day of treatment were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had a history of clinically significant lung diseases; uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals; clinically active brain metastases; unresolved toxicities from previous anticancer therapy; or a known hypersensitivity to substances in DB-1303.

Reference

DualityBio announces DB-1303 granted fast track designation by the U.S. Food and Drug Administration (FDA) for the treatment of advanced, recurrent or metastatic endometrial carcinoma with HER2 overexpression. News release. Duality Biologics. January 20, 2023. Accessed January 23, 2023. prn.to/3JdgP82