ADC Drug Candidate Enters Phase 3 Trial for the Treatment of HER2-Low Breast Cancer


The candidate has already demonstrated anti-tumor activity in chemotherapy-naïve patients.

Investigators are conducting a phase 3 trial to evaluate BNT323/DB-1303 (BioNTech, DualityBio), a third-generation topoisomerase-1 inhibitor-based antibody drug conjugate (ADC), for patients with hormone receptor positive (HR+) and human epidermal growth factor receptor 2 (HER2)-low (HER2-low) breast cancer (BC) who have progressed past primary therapy.

In an ongoing phase 1/2 study (NCT05150691), the objective response rate (ORR) among patients treated with BNT323/DB-1303 is 38.5% and the disease control rate is 84.6%. The drug candidate also appears to be well-tolerated and safe for patients with advanced and metastatic solid BC tumors.

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“BNT323/DB-1303 has been designed with the aim to combine the selectivity of antibodies with the cancer cell-killing properties of chemotherapy, thereby aiming to minimize the toxicity of the chemotherapeutic agents for patients,” said Özlem Türeci, MD, chief medical officer and co-founder of BioNTech, in a recent press release.

BC is the number 1 diagnosed cancer globally; approximately 40% to 45% of women diagnosed with BC will develop metastatic and advanced HR+/HER2-low BC, which is characterized by a low expression of the HER2 protein on the surface of cancer cells. Unfortunately, malignant disease remains a primary cause of cancer-related death among women.

HER2-directed therapies are a viable treatment option for patients with medium or high HER2 expression, but they are less effective for patients with HER2-low disease. In the search for new treatment options, ADCs have emerged as a possible candidate.

“Our objective is to further expand the impact of HER2-targeted ADC therapies to chemotherapy-naïve patients in metastatic disease stage who express HER2 at low levels at earliest possible treatment lines,” Türeci said in the press release. “[We are] seeking to extend the therapeutic window and improve outcomes for these patients.”

In a global, multi-center, open-label, and randomized phase 3 trial (NCT06018337), investigatorswill evaluate BNT323/DB-1303 in 532 patients with HR+ and HER2-low metastatic and advanced BC whose cancer has progressed while the patient is on hormone therapy. Investigators will compare the safety and efficacy of the ADC with standard-of-care single-agent chemotherapy in patients located across 233 clinical sites.

The primary endpoint of this phase 3 trial will be progression-free survival (PFS) and secondary endpoints are overall survival, ORR, duration of response, and safety.

BNT323/DB-1303 is a topoisomerase-1 inhibitor that targets HER2, a protein that is expressed on solid tumors and promotes the growth and spread of cancer cells. In 2023, the FDA had granted BNT323/DB-1303 Fast Track and Breakthrough Therapy designation for the treatment of endometrial cancer.

“The initiation of the phase 3 trial marks an important step in the development of our next-generation ADC candidate with the first indication progressing into pivotal evaluation,” said Vivian Gu, MD, chief medical officer, DualityBio, in the press release.


BioNTech and DualityBio Initiate Pivotal Phase 3 Trial Of Antibody-Drug Conjugate Candidate BNT323/DB-1303 in Metastatic Breast Cancer. BioNTech. January 22, 2024. Accessed on January 23, 2024.

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