FDA Fast Tracks Promising New ADC in mCRPC


BNT324/DB-1311 gained fast track designation from the FDA in unresectable advanced or metastatic castration-resistant prostate cancer who have progressed after standard treatments.

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  • The FDA has granted a fast track designation to BNT324/DB-1311, an antibody-drug conjugate (ADC), for the treatment of patients with unresectable advanced or metastatic castration-resistant prostate cancer (mCRPC) who have progressed after standard treatments.
  • BNT324/DB-1311 targets the B7-H3 protein, which is overexpressed in various solid tumors.
  • Preliminary phase 1/2 trial (NCT05914116) data indicate the drug's efficacy and manageable toxicity.

A fast track designation has been granted from the FDA to BNT324/DB-1311, an ADC, for the treatment of patients with unresectable advanced or metastatic CRPC who have progressed on or after standard systemic regimens.1

BNT324/DB-1311 is currently undergoing evaluation in a phase 1/2 trial in patients with advanced solid tumors. Preliminary data from this study have demonstrated efficacy and manageable toxicity.

“The FDA’s decision is a recognition of the potential of our B7-H3–targeting ADC candidates for the treatment of [patients with] advanced CRPC. [Although] patients with metastatic prostate cancer initially respond to hormone therapy, most patients progress after 18 to 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 mCRPC is only around 36%,” Özlem Türeci, MD, chief medical officer and co-founder of BioNTech, stated in a news release.

BNT324/DB-1311 is a next-generation ADC which targets the transmembrane glycoprotein B7-H3. B7-H3 is an immune checkpoint protein that is overexpressed in various solid tumors and is associated with disease progression and poor prognosis.

The ADC also has a topoisomerase I inhibitor payload. In preclinical studies, BNT324/DB-1311led to antitumor activity across a variety of solid tumor models.

“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,” Türeci said in the press release.

3d rendered medically accurate illustration of prostate cancer: © SciePro - stock.adobe.com

3D rendered medically accurate illustration of prostate cancer: © SciePro - stock.adobe.com

About the Phase 1/2 Trial of BNT324/DB-1311

In this first-in-human, multicenter, open-label dose-escalation and -expansion study, patients aged 18 years of age or older with histologically or cytologically confirmed, unresectable advanced or metastatic solid tumors were enrolled if they had disease that relapsed or progressed on or after standard systemic treatments.2

Patients were required to be intolerable to standard treatment, have no standard treatment available, have at least 1 measurable lesion per RECIST v1.1 criteria, and have a life expectancy of at least 3 months, Moreover, an ECOG performance status of 0 or 1 and a left ventricular ejection fraction of at least 50% were requirements for enrollment in the study.

Phase 1 of the trial adopted an accelerated titration at first dose level followed by a 3+3 design to identify the maximum tolerated dose and/or recommended phase 2 dose. Phase 2a is the dose-expansion portion of the study aimed at confirming the safety, tolerability, and efficacy of the agent as a monotherapy in the treatment of selected malignant solid tumors.

In cohort 4 of phase 2a, patients with CRPC are being enrolled if they have pathologically documented metastatic adenocarcinoma of the prostate. Here, progressive mCRPC is defined as castrate levels of serum testosterone less than 50 ng/dL and progressive disease per Prostate Cancer Working Group 3 criteria.

These patients must have received prior docetaxel, either before or after androgen receptor-targeted therapy, and have received prior novel hormone therapy. Docetaxel rechallenge is also permitted for enrollment.

During the dose-escalation portion of the study, investigators are giving BNT324/DB-1311 to patients with mCRPC, small cell lung cancer, non–small cell lung cancer, esophageal squamous cell carcinoma, melanoma, and other tumors, at 1 of 5 dose levels on day 1 of each 3-week cycle.

The primary end points of phase 1 are to identify the proportion of patients with dose-limiting toxicities, identify the proportion of patients with treatment-emergent adverse effects (TEAEs) and serious AEs, and determine the maximum tolerated dose and recommended phase 2 dose. For phase 2, the primary end points are to evaluate the rate of TEAEs and serious AEs and objective response rate per RECIST v1.1 criteria. Evaluation of pharmacokinetics is a secondary end point.

1. BioNTech and DualityBio receive FDA fast track designation for antibody-drug conjugate candidate BNT324/DB-1311 in prostate cancer. News release. BioNTech. June 24, 2024. Accessed July 8, 2024. https://tinyurl.com/mwnu3nj7
2. A study of DB-1311 in advanced/​metastatic solid tumors. ClinicalTrials.gov. Updated September 13, 2023. Accessed July 8, 2024. https://clinicaltrials.gov/study/NCT05914116
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