A Phase III Trial of BNT324 Versus Docetaxel in Metastatic Castration-resistant Prostate Cancer

A Phase III, Randomized, Open-label Trial of BNT324 Versus Docetaxel With Prednisone/Prednisolone in Metastatic Castration-resistant Prostate Cancer

This study will test whether BNT324 is safe and works better against metastatic castration-resistant prostate cancer (mCRPC) than the current standard of care (SoC) chemotherapy, which is docetaxel (given together with the steroid medicines prednisone or prednisolone). The study will include participants with mCRPC that have been previously treated with androgen receptor pathway inhibitor, but with no previous taxane-based systematic chemotherapy for mCRPC.

The main goals of this study are:

• To find out if BNT324 helps participants live longer without their cancer getting worse (radiographic progression-free survival [rPFS]).
• To find out if BNT324 helps participants live longer overall (overall survival [OS]).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: BNT324; Drug: Prednisone/prednisolone

Detailed Description

The study consists of a screening period (up to 28 days), a treatment period with 21-day cycles, and an after-treatment period that includes a 30-day safety follow-up period and a long-term survival follow-up period.

Treatment continues until the cancer clearly gets worse (in scans, based on blinded independent central review [BICR] assessment or investigator's decision), side effects become unacceptable, the participant chooses to stop, or the study ends.

Participants are put into one of two groups in a 1:1 ratio, which means they will have an equal chance to be in either treatment group, i.e., BNT324 group, or docetaxel plus prednisone/prednisolone group (current SoC). An independent committee will help ensure participant safety, by regularly reviewing safety and early results.

For each participant, the treatment and follow-up periods are projected to be up to ~58 months.

• Study Type: Interventional
• Enrollment (Estimated): 736
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• United States
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Recruiting
      • Maryland Oncology Hematology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Austin, Texas, United States, 78731
      • Recruiting
      • Texas Oncology South Austin
    • Houston, Texas, United States, 77024
      • Recruiting
      • Texas Oncology Gulf Coast
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology, P.A. - Tyler

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Are male adults (defined as ≥18 years of age or of an acceptable age according to local regulations at the time of giving informed consent).

• Must have documented progressive prostate cancer based on at least one of the following criteria:

  • Serum/plasma PSA progression, by local laboratory, defined as two consecutive increases in PSA over a previous reference value, each measured sequentially at least 1 week apart. The PSA value at screening is required to be ≥1.0 ng/mL.
  • Radiographic soft tissue progression as per PCWG3-modified RECIST v1.1.
  • Radiographic progression of bone disease: evaluable disease or new bone lesion(s) by bone scan per PCWG3 criteria.
• Had previously received one or two prior androgen receptor pathway inhibitor treatments and experienced disease progression during or after a minimum of 8 weeks of therapy.
• Must not have received systemic cytotoxic chemotherapy, including taxane-based chemotherapy, for mCRPC.
• Must have had prior orchiectomy and/or have ongoing androgen-deprivation therapy and a castrate-level of serum/plasma testosterone (<50 ng/dL or <1.7 nmol/L). Participant being treated with luteinizing hormone-releasing hormone agonists or antagonists must continue such treatment throughout the study.
• Must have an Eastern Cooperative Oncology Group performance score of 0 or 1.

Key Exclusion Criteria:

• Have received prior treatment with B7-H3 targeted therapy, including B7-H3 ADCs.
• Have uncontrolled or significant cardiovascular disease, as defined in the protocol.
• Have a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids or have current ILD/pneumonitis.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BNT324	Drug: BNT324; Intravenous infusion; Other Names: DB-1311
Active Comparator: Docetaxel plus prednisone/ prednisolone	Drug: Docetaxel; Intravenous infusion; Drug: Prednisone/prednisolone; Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rPFS assessed by BICR	By arm. rPFS is defined as time from randomization to radiographic disease progression per Prostate Cancer Working Group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria, or death from any cause, whichever occurs first.	From randomization to end of study, i.e., up to 58 months
OS	By arm. OS is defined as time from randomization to death from any cause.	From randomization to end of study, i.e., up to 58 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first subsequent therapy (TFTS)	By arm. TFST is defined as time from randomization to initiation of the first subsequent systemic anticancer therapy or death, whichever occurs first.	From randomization to end of study, i.e., up to 58 months
Objective response rate (ORR)	By arm. ORR is defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per PCWG3-modifed RECIST v1.1 as assessed by BICR) is observed as best overall response.	From randomization to end of study, i.e., up to 58 months
Duration of response (DOR)	By arm. DOR is defined as time from first objective response (confirmed CR or PR per PCWG3-modified RECIST v1.1 criteria as assessed by BICR) to first occurrence of objective tumor progression (progressive disease per PCWG3-modified RECIST v1.1 criteria as assessed by BICR) or death from any cause, whichever occurs first.	From randomization to end of study, i.e., up to 58 months
Time to pain progression (TTPP)	By arm. TTPP is defined as time from randomization to pain progression as determined by Brief Pain Inventory-Short Form Item 3 "worst pain in 24 hours" and opiate analgesic use (Analgesic Quantification Algorithm score).	From randomization to safety follow-up visit (30 days after the last dose), i.e., up to 58 months
rPFS as assessed by investigator	By arm. rPFS is defined as time from randomization to radiographic disease progression per PCWG3-modified RECIST v1.1 criteria, or death from any cause, whichever occurs first.	From randomization to end of study, i.e., up to 58 months
Time to first symptomatic skeletal-related event (SSRE)	By arm. Time to first SSRE is defined as time from randomization to first occurrence of any of the following SSREs: Use of external beam radiation therapy to prevent or relieve skeletal symptoms.; New symptomatic pathologic bone fracture (vertebral or non-vertebral).; Spinal cord compression.; Tumor-related orthopedic surgical intervention.	From randomization to end of study, i.e., up to 58 months
Time to prostate-specific antigen (PSA) progression (by central lab testing results)	By arm. Time to PSA progression is defined as time from randomization to PSA progression per PCWG3 criteria.	From baseline to end of treatment visit, i.e., up to 58 months
PSA response (by central lab testing results)	By arm. PSA response is defined as having a post-baseline PSA reduction ≥50% from baseline with a consecutive confirmation assessment at least 3 weeks later per PCWG3 criteria.	From baseline to end of treatment visit, i.e., up to 58 months
Number and percentage of participants with treatment-emergent adverse events (TEAEs) including Grade ≥3, serious, and fatal TEAEs	TEAEs by relationship and by arm.	From the start of study treatment until 30 days after the last dose of study treatment or until start of new systemic anticancer therapy, whichever occurs first, i.e., up to 58 months
Number and percentage of participants with dose interruptions, reductions or discontinuations of study treatment due to TEAEs	By arm.	From the start of study treatment until 30 days after the last dose of study treatment or until start of new systemic anticancer therapy, whichever occurs first, i.e., up to 58 months

Collaborators and Investigators

• Sponsor: BioNTech SE
• Collaborators: DualityBio Inc.; BioNTech (Shanghai) Pharmaceuticals Co., Ltd.
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2026
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031

Study Registration Dates

• First Submitted: January 23, 2026
• First Submitted That Met QC Criteria: January 23, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Chemotherapy; mCRPC; Steroids; Antibody-drug conjugate (ADC); BNT324 (DB-1311); Standard of care (SoC)
• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Polycyclic Compounds; Taxoids; Cyclodecanes; Diterpenes; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Pregnadienediols; Docetaxel; Prednisone; Prednisolone
• Other Study ID Numbers: BNT324-03; 2025-524445-27-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No