BioNTech, DualityBio unveil partnered ADC for solid tumors

Duality Biologics and BioNTech have reported promising interim data from one of their partnered antibody-drug conjugates (ADCs). In a preliminary analysis from their trial, it was observed that nearly one-third of the treated patients showed unconfirmed responses.

In a group of 238 patients who were assessable with at least one post-baseline tumor evaluation, 32.4% displayed an unconfirmed overall response, while the disease control rate was 82.4%. Specifically, among the 73 patients with small-cell lung cancer, the unconfirmed overall response rate (ORR) was 56.2% and the disease control rate (DCR) was 89%.

For patients with castration-resistant prostate cancer (CRPC), the data on radiographic progression-free survival (rPFS) are not fully mature yet. However, results presented at the ESMO Asia conference in Singapore reveal that the median rPFS was 7.2 months, with a six-month rPFS rate of 94.7%.

This ongoing Phase 1/2a basket trial is evaluating various doses of the drug BNT324, also known as DB-1311, across 277 heavily pretreated patients. Early positive responses were also noted in patients with cervical cancer, hepatocellular carcinoma, head and neck squamous cell carcinoma, and melanoma. About 61% of the trial participants had received two or more prior lines of therapy.

Further data collection is necessary, as the study primarily focuses on safety and objective response rate, which requires confirmation of the responses. Secondary endpoints include the duration of response, disease control rate, progression-free survival, and overall survival.

BNT324 is a topoisomerase I inhibitor-based conjugate that targets the transmembrane glycoprotein B7-H3. Various companies are investigating B7-H3 as a therapeutic target, including Merck, which is developing ifinatamab deruxtecan. Notably, a trial of MacroGenics’ B7-H3-targeting antibody in head and neck cancer was halted following several patient deaths.

According to DualityBio, their candidate exhibited a “manageable” safety profile across all evaluated patients and tumor types in this early trial. The most common treatment-related side effects included nausea, decreased neutrophil count, anemia, decreased white blood cell count, decreased appetite, and decreased platelet count.

BNT324 has been granted US fast track status for advanced/unresectable or metastatic CRPC and orphan drug designation for advanced or metastatic esophageal squamous cell carcinoma. This drug is one of three clinical-stage ADCs being developed by BioNTech and DualityBio under their partnership established in April 2023.

In addition, they plan to test some of these ADCs in combination with a bispecific antibody that targets PD-L1 and VEGF-A, known as BNT327 or PM8002, in solid tumors. This bispecific antibody is being co-developed by BioNTech and Biotheus.