BioNTech and DualityBio Launch Phase 3 Trial for Metastatic Breast Cancer ADC BNT323/DB-1303

BioNTech and Duality Bio have initiated a crucial Phase 3 clinical trial to evaluate the efficacy and safety of their next-generation antibody-drug conjugate (ADC), BNT323/DB-1303, targeting the HER2 protein in metastatic breast cancer patients. The study is set to recruit 532 individuals with hormone receptor-positive and HER2-low metastatic breast cancer that has progressed on hormone therapy. Initially, the trial will take place in China, with subsequent expansion to the United States, Europe, and other regions.

Breast cancer is the most frequently diagnosed cancer globally and the primary cause of cancer-related deaths among women. The subtype characterized by the presence of hormone receptors and low levels of HER2 protein on the cancer cell surface is common in advanced stages of the disease. While HER2 has been a successful target for treating certain breast cancers, therapies have been ineffective for patients with low HER2 expression. However, new ADCs may extend the benefits of HER2-targeted treatments to HER2-low tumors.

The Phase 3 trial, an open-label, randomized study, will compare BNT323/DB-1303 against standard chemotherapy in chemotherapy-naïve patients. The primary goal is to measure progression-free survival, with secondary endpoints encompassing overall survival, response rates, and safety.

Prof. Özlem Türeci, BioNTech's Chief Medical Officer, highlighted the innovative design of BNT323/DB-1303, which combines antibody selectivity with the cytotoxic effects of chemotherapy, aiming to reduce chemotherapeutic toxicity for patients. The trial's initiation is a significant step in the development of this ADC candidate, with preliminary data from a Phase 1/2 study showing promising anti-tumor activity and a manageable safety profile.

Vivian Gu, DualityBio's Chief Medical Officer, expressed excitement about advancing the candidate into pivotal evaluation, emphasizing the potential of this differentiated ADC. The trial builds on positive data from a Phase 1/2 study, which reported an objective response rate of 38.5% and a disease control rate of 84.6% in heavily pretreated HER2-low breast cancer patients.

The collaboration between BioNTech and DualityBio aims to expedite the development of innovative ADC therapeutics for solid tumors. BioNTech retains global commercial rights, excluding certain regions where DualityBio holds the rights. The BNT323/DB-1303 program has received Fast Track and Breakthrough Therapy designations from the FDA for the treatment of endometrial cancer.

BNT323/DB-1303 is a third-generation topoisomerase-1 inhibitor-based ADC developed from DualityBio’s proprietary platform. It has shown potential in targeting HER2 receptors on solid tumors, irrespective of expression levels, with a manageable safety profile. The candidate is currently under evaluation in ongoing Phase 1/2 and pivotal Phase 3 studies.

BioNTech is a biopharmaceutical company focusing on novel therapies for cancer and other serious diseases, utilizing computational discovery and therapeutic drug platforms. Their oncology pipeline includes mRNA-based therapies, CAR T cells, protein-based therapeutics, and small molecules. DualityBio is a clinical-stage company specializing in the discovery and development of next-generation ADC therapeutics for cancer and autoimmune diseases, with several innovative product candidates in clinical and preclinical stages.