FDA Grants Fast Track Designation to DB-1303 for HER2-Overexpressed Advanced/Recurrent Endometrial Cancer

The FDA has granted a fast track designation to DB-1303 for the treatment of patients with advanced, recurrent or metastatic endometrial cancer with HER2 overexpression who have progressed on or after standard systemic therapy.¹

“The FDA’s decision to grant fast track designation 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, chief executive officer of DualityBio, said in a press release. “We are committed to advance this investigational drug to help those patients who are suffering from cancers. We will work closely with clinical investigators and health authorities to unlock the full potential of DB-1303 in patients with malignant tumors.”

HER2 is overexpressed in approximately 60% to 70% of high-grade endometrial cancers, rendering it an attractive target for treatment. However, limited options exist for patients with recurrent or metastatic disease who have progressed on prior platinum-based therapy with or without immunotherapy.

DB-1303 is a novel, third-generation antibody-drug conjugate (ADC) comprised of an anti-HER2 monoclonal antibody, enzymatically cleavable peptide-linker, and proprietary topoisomerase I inhibitor P1003. The ADC is designed to have potent antitumor activity and bystander killing effect, high plasma stability, low free payload in circulation, and wide therapeutic index.

In HER2-positive and HER2-low tumor models, DB-1303 displayed favorable antitumor activity, safety, and an expanded therapeutic window.

The agent is under evaluation in an ongoing phase 1/2a trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic, HER2-positive or HER2-low solid tumors.²

To be eligible for enrollment, patients must have disease that is refractory to or intolerable with standard treatment, or for which no standard treatment is available; at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1; a left ventricular ejection fraction of 50% or greater by ECHO or MUGA; adequate organ function; and life expectancy of at least 3 months.

HER2 status will be confirmed with a pre-existing diagnosis, test on resected tumor samples, or fresh tumor biopsy.

The multicenter, non-randomized, open-label, multiple-dose, first-in-human study consists of two parts. Part 1 will use an accelerated titration at the first dose level followed by a 3+3 design to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the agent. Part 2 will serve as a dose-expansion phase to determine the safety, tolerability, and efficacy in selected malignant solid tumors at the MTD/RP2D.

References

1. 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. https://prn.to/3HrtDq8
2. A study of DB-1303 in advanced/metastatic solid tumors. ClinicalTrials.gov. Updated January 10, 2023. Accessed January 23, 2023. https://clinicaltrials.gov/ct2/show/NCT05150691