Novel B7H3 Antibody-Drug Conjugate Shows Strong Efficacy in Cervical and Ovarian Cancers
Key Insights
DB-1311/BNT324 (search), a novel B7H3 (search)-targeted antibody-drug conjugate, demonstrated a 42.4% overall response rate in previously treated cervical cancer (search) patients with a median progression-free survival of 7.0 months.
In platinum-resistant ovarian cancer (search) patients, the ADC achieved a 53.3% overall response rate and 9.5 months median progression-free survival, showing efficacy regardless of prior treatment history.
The treatment showed consistent activity across different histological subtypes and prior therapy lines, with manageable safety profile and low treatment discontinuation rates.
Treatment with DB-1311/BNT324 (search), a novel B7H3 (search) antibody-drug conjugate (ADC), demonstrated significant antitumor activity in patients with previously treated cervical cancer (search) and platinum-resistant ovarian cancer (search) (PROC), according to findings from a phase 1/2 trial presented at the 2026 Society of Gynecologic Oncology (search) Annual Meeting on Women's Cancer.
The results, presented by Dr. Ira S. Winer from Wayne State University School of Medicine, showed encouraging response rates and progression-free survival outcomes across both cancer types, regardless of prior treatment history or histological subtype.
Cervical Cancer Efficacy Results
Across 33 patients with second- and third-line cervical cancer (search), DB-1311/BNT324 (search) achieved an overall response rate (ORR) of 42.4% (95% CI, 25.5%-60.8%), with a disease control rate (DCR) of 81.8% (95% CI, 64.5%-93.0%) and median progression-free survival (PFS) of 7.0 months (95% CI, 4.4-not evaluable).
The treatment showed consistent efficacy across different histological subtypes. In patients with squamous histology (n=21), the ORR was 42.9% (95% CI, 21.8%-66.0%), DCR was 81.0% (95% CI, 58.1%-94.6%), and median PFS was 7.0 months. For adenocarcinoma histology (n=11), the ORR reached 45.5% (95% CI, 16.8%-76.6%), with a DCR of 81.8% and median PFS of 8.4 months.
Treatment line did not significantly impact efficacy. Second-line patients (n=12) achieved a 50.0% ORR and 8.7 months median PFS, while third-line patients (n=20) demonstrated a 40.0% ORR and 7.0 months median PFS.
Prior therapy history also did not diminish treatment effectiveness. Patients who received prior immunotherapy (n=20) showed an ORR of 35.0% and median PFS of 6.7 months, while those with prior bevacizumab treatment (n=22) achieved a 45.5% ORR and 8.2 months median PFS.
Platinum-Resistant Ovarian Cancer Outcomes
The PROC cohort (n=30) demonstrated even stronger response rates, with an ORR of 53.3% (95% CI, 34.3%-71.7%), DCR of 83.3% (95% CI, 65.3%-94.4%), and median PFS of 9.5 months (95% CI, 6.3-not evaluable). Best overall responses included complete response in 6.7% of patients, partial response in 46.7%, stable disease in 30.0%, and progressive disease in 10.0%.
Among patients with prior bevacizumab exposure (n=22), the ORR was 54.5% with a median PFS of 9.5 months. Those who received prior PARP inhibitors (n=19) achieved a 57.9% ORR and 7.2 months median PFS.
In the subset of patients with longest follow-up (n=12; median follow-up 12.1 months), the ORR reached 58.3%, with a median duration of response of 8.0 months and median PFS of 9.5 months.
Trial Design and Patient Population
The phase 1/2 trial enrolled patients aged 18 years or older with either recurrent or metastatic cervical cancer (search) with 1-2 lines of prior systemic treatment, or PROC with 1-3 prior treatment lines. Eligible patients required at least one measurable lesion per RECIST v1.1 criteria, ECOG performance status of 0-1, and adequate organ function. Exclusion criteria included prior B7H3 (search)-targeted therapy and prior topoisomerase-1 ADC treatment.
DB-1311/BNT324 (search) was administered as an intravenous infusion on day 1 of each 3-week cycle at varying dose levels.
Safety Profile
Treatment-related adverse events (TRAEs) of any grade occurred in 87.8% of patients, with grade 3 or higher TRAEs in 54.1%. The safety profile was similar between cancer types: cervical cancer (search) patients experienced any TRAE and grade 3+ TRAEs in 86.5% and 56.8% respectively, while PROC patients had rates of 89.2% and 51.4%.
Dose reductions due to TRAEs were required in 27.0% of cervical cancer (search) patients and 16.2% of PROC patients. Treatment discontinuation due to adverse events occurred in only 2.7% of patients in both cohorts. Notably, no treatment-related deaths were reported.
"[We saw] encouraging [overall response rate] and [progression-free survival] in patients with previously treated cervical cancer (search) or PROC, regardless of prior treatment or histology," said Winer.
The investigators noted that a global phase 2 trial of DB-1311/BNT324 (search) plus pumitamig (search) is currently enrolling patients with cervical cancer (search) or PROC, suggesting continued development of this promising therapeutic approach.