Novel B7H3 ADC Yields Responses in Cervical Cancer and Platinum-Resistant Ovarian Cancer

Treatment with DB-1311/BNT324, a novel B7H3 antibody-drug conjugate (ADC), resulted in antitumor activity among patients with previously treated cervical cancer or platinum-resistant ovarian cancer (PROC), regardless of prior treatment or histology, according to findings from the phase 1/2 trial (NCT05914116).¹

These data were presented by Ira S. Winer, MD, PhD, professor and clinician educator in the Department of Oncology at Wayne State University School of Medicine, at the 2026 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO).

How efficacious was DB-1311/BNT324 in cervical cancer?

Across patients with second- and third-line cervical cancer (n = 33), the overall response rate (ORR) was 42.4% (95% CI, 25.5%-60.8%), the disease control rate (DCR) was 81.8% (95% CI, 64.5%-93.0%), and the median progression-free survival (PFS) was 7.0 months (95% CI, 4.4-not evaluable [NE]). Of those with squamous histology (n = 21), the ORR, DCR, and median PFS were 42.9% (95% CI, 21.8%-66.0%), 81.0% (95% CI, 58.1%-94.6%), and 7.0 months (95% CI, 4.4-NE), respectively. In those with adenocarcinoma histology (n = 11), the ORR, DCR, and median PFS were 45.5% (95% CI, 16.8%-76.6%), 81.8% (95% CI, 48.2%-97.7%), and 8.4 months (95% CI, 4.1-NE).

In those with second-line disease (n = 12), the ORR, DCR, and median PFS were 50.0% (21.1%-78.9%), 91.7% (61.5%-99.8%), and 8.7 months (4.4-NE). In those with third-line disease (n = 20), the ORR, DCR, and median PFS were 40.0% (95% CI, 19.1%-64.0%), 80.0% (95% CI, 56.3%-94.3%), and 7.0 months (95% CI, 3.9-NE), respectively.

When stratified by prior treatment, those who received prior immunotherapy (n = 20) demonstrated an ORR of 35.0% (95% CI, 15.4%-59.2%), a DCR of 80.0% (95% CI, 56.3%-94.3%), and a median PFS of 6.7 months (95% CI, 1.9-8.2). Those who received prior bevacizumab (Avastin; n = 22) achieved an ORR of 45.5% (95% CI, 24.4%-67.8%), a DCR of 86.4% (95% CI, 65.1%-97.1%), and a median PFS of 8.2 months (95% CI, 4.4-NE).

What were the efficacy outcomes with DB-1311/BNT324 in PROC?

Across the entire PROC cohort (n = 30), the ORR, DCR, and median PFS were 53.3% (95% CI, 34.3%-71.7%), 83.3% (95% CI, 65.3%-94.4%), and 9.5 months (95% CI, 6.3-NE), respectively. Best overall responses were complete response (CR) in 6.7%, partial response (PR) in 46.7%, stable disease (SD) in 30.0%, and progressive disease (PD) in 10.0%.

Across patients who received prior bevacizumab (n = 22), the ORR, DCR, and median PFS were 54.5% (95% CI, 32.2%-75.6%), 77.3% (95% CI, 54.6%-92.2%), and 9.5 months (95% CI, 6.3-NE). Best overall response was CR in 0%, PR in 54.5%, SD in 22.7%, and PD in 13.6%.

Across those who received prior PARP inhibitors (n =19), the ORR, DCR, and median PFS were 57.9% (95% CI, 33.5%-79.8%), 84.2% (95% CI, 60.4%-96.6%), and 7.2 months (95% CI, 6.3-NE), respectively. Best overall response was CR in 5.3%, PR in 52.6%, SD in 26.3%, and PD in 15.8%.

Notably, across patients with the longest follow-up (n = 12; median follow-up, 12.1 months), the ORR was 58.3%, the median duration of response was 8.0 months, and the median PFS was 9.5 months.

“[We saw] encouraging [overall response rate (ORR)] and [progression-free survival (PFS)] in patients with previously treated cervical cancer or PROC, regardless of prior treatment or histology,” said Winer.

How was the phase 1/2 trial designed?

Eligible patients for the trial were 18 years or older with either recurrent or metastatic cervical cancer with 1 or 2 lines of prior systemic treatment or PROC with 1 to 3 prior lines of systemic treatment. Patients also had at least 1 measurable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function. Exclusion criteria included prior B7H3-targeted therapy and prior topoisomerase-1 ADC.

DB-1311/BNT324 was administered as an intravenous infusion on day 1 of each cycle every 3 weeks at varying dose levels.²

How safe was DB-1311/BNT324 treatment for these populations?

Any treatment-related adverse event (TRAE) occurred in 87.8% of patients, with grade 3 or higher TRAEs occurring in 54.1%. Among those with cervical cancer, any TRAE and grade 3 or higher TRAEs occurred in 86.5% and 56.8%, respectively. Among those with PROC, those rates were 89.2% and 51.4%, respectively.

Notably, dose reductions and treatment discontinuation due to TRAEs occurred in 27.0% and 2.7% of the cervical cancer population and 16.2% and 2.7% of the PROC population. No patients died due to a TRAE.

The investigators also noted that a global phase 2 trial (NCT06953089) of DB-1311/BNT324 plus pumitamig is currently enrolling patients with cervical cancer or PROC.

Disclosures: Winer cited research funding with Jazz Pharmaceuticals and a financial relationship with no funding with Ernexa Medical Advisory Board.

References

1. Winer IS, Gao B, Chang CL, et al. A global, phase 1/2 study of DB‑1311/BNT324 (a novel B7H3 ADC) monotherapy in patients with previously treated advanced cervical cancer or platinum-resistant recurrent ovarian cancer: outcomes by prior treatment. Presented at the 2026 SGO Annual Meeting on Women’s Cancer; April 10-13, 2026; San Juan, PR.
2. A phase 1/​2a study of DB-1311/​BNT324 in advanced/​metastatic solid tumors. ClinicalTrials.gov. Updated November 21, 2025. Accessed April 12, 2026. https://tinyurl.com/y7fbh5a9