FDA awards fast track designation to BNT324/DB-1311 in mCRPC

The FDA has granted a fast track designation to the antibody drug conjugate (ADC) candidate BNT324/DB-1311 for patients with advanced/unresectable or metastatic castration-resistant prostate cancer (mCRPC) whose tumors have progressed on standard systemic regimens, announced BioNTech SE and Duality Biologics in a news release.¹

BNT324/DB-1311 targets B7-H3, an immune checkpoint molecule.

Fast track designation is awarded to new drugs and vaccines that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. With this designation, the development process for BNT324/DB-1311 can benefit from more frequent engagement with the FDA to support an expedited review process.

“The FDA’s decision is a recognition of the potential of our B7-H3-targeting ADC candidate for the treatment of advanced CRPC. While patients with metastatic prostate cancer initially respond to hormone therapy, most patients progress after 18-24 months and develop CRPC, an advanced form of prostate cancer, leading to a poor prognosis for these patients. The 5-year survival rate for patients with metastatic CRPC is only around 36%,” said Prof. Özlem Türeci, MD, chief medical officer and co-founder of BioNTech, in the news release.¹ “We are committed to further advancing BNT324/DB-1311 with our partner DualityBio and believe that a targeted ADC immunotherapy approach has the potential to improve outcomes for patients at advanced stages of the disease.”

BNT324/DB-1311 is a topoisomerase-I-inhibitor-based ADC that targets B7-H3, an immune checkpoint molecule.

The fast track designation for BNT324/DB-1311 is supported by preliminary safety and efficacy data from an ongoing phase 1/2 trial (NCT05914116) of the ADC in patients with advanced/metastatic solid tumors, including mCRPC. According to the news release, initial data from the trial has shown a manageable safety profile and preliminary anti-tumor activity with BNT324/DB-1311 in these patients.

In total, the study plans to enroll approximately 90 patients with advanced/metastatic CRPC, non-small cell lung cancer, esophageal squamous cell carcinoma, melanoma, and other solid tumors in the phase 1 portion of the trial and 190 patients in the phase 2a portion.² Patients will be enrolled across clinical trial sites in the US, Australia, China, and Taiwan.

Those included in the study will receive intravenous DB-1311 as a monotherapy until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent. To be eligible for the trial, patients must have tumors that have relapsed or progressed on or after standard systemic therapy, are intolerable to standard therapy, or for which no standard therapy is available; have an ECOG PS score of 1 or below; and have adequate organ function.

The phase 1 portion of the study will include up to 5 ascending dose levels of DB-1311 in a 3+3 design. The primary outcome measures are safety and the determination of a maximum tolerated dose and a recommended dose level for phase 2 of the trial. For the phase 2a portion, the trial will further explore the safety, efficacy, and pharmacokinetics of the therapy in patients with solid tumors.³

With the fast track designation for BNT324/DB-1311 in mCRPC, 3 of BioNTech’s ADC candidates have now received such designations, including the BNT323/DB-1303 program for endometrial cancer in 2023 and the BNT325/DB-1305 (targetingtrophoblast cell-surface antigen 2) program in platinum-resistant ovarian epithelial cancer in January 2024.

Vivian Gu, MD, chief medical officer at DualityBio, concluded in the news release,¹ “BNT324/DB-1311 is the third asset in our strategic collaboration which has received FDA Fast Track designation, highlighting the potential of the candidate to fill an unmet medical need for novel treatment options for B7-H3 expressing cancers. Preliminary data from our ongoing phase 1/2 trial has demonstrated antitumor activity and a manageable safety profile of BNT324/DB-1311 in patients with advanced solid tumors. With the designation and support by the FDA, we seek to expedite further development of BNT324/DB-1311.”

References

1. BioNTech and DualityBio receive FDA Fast Track Designation for antibody-drug conjugate candidate BNT324/DB-1311 in prostate cancer. News release. BioNTech SE. Published online and accessed June 24, 2024. https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-receive-fda-fast-track-designation

2. Cheng Y, Lisberg A, Lemech C, et al. CT165 / 16 - A phase 1/2a, multicenter, open-label, first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1311 (a B7-H3-targeting ADC) in patients with advanced/metastatic solid tumors. Presented at: AACR Annual Meeting. April 5-10, 2024. Abstract CT165

3. A study of DB-1311 in advanced/metastatic solid tumors. ClinicalTrials.gov. Last updated September 13, 2023. Accessed June 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05914116