BNT324

Shows activity

Also known as:

DB-1311

Cancer types include:

cervical cancer esophageal cancer head and neck cancer liver cancer melanoma

TrialFetch AI Analysis

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Overview

BNT324 (DB-1311) is an investigational antibody–drug conjugate (ADC) targeting B7-H3, being co-developed by BioNTech and DualityBio. It is in a global first‑in‑human Phase 1/2a trial (NCT05914116) across multiple advanced solid tumors, with preliminary efficacy signals in small cell lung cancer (SCLC), non‑small cell lung cancer (NSCLC), and castration‑resistant prostate cancer (CRPC). In June 2024 the FDA granted Fast Track designation for CRPC; in July 2024 it received Orphan Drug designation for esophageal squamous cell carcinoma (ESCC). (clinicaltrials.biontech.com)

Mechanism of action

Target: B7-H3 (CD276), an immune checkpoint protein overexpressed in many solid tumors with limited expression in normal tissues and associated with poor prognosis. (oncologypro.esmo.org)
Construct: Humanized anti–B7‑H3 IgG1 linked via a cleavable maleimide tetrapeptide linker to a proprietary DNA topoisomerase‑I inhibitor payload (also described preclinically as P1021); drug‑to‑antibody ratio ≈6. (aacrjournals.org)
Dosing/PK (Phase 1/2a): 3–12 mg/kg IV every 3 weeks; maximum tolerated dose (MTD) 9 mg/kg. ADC and payload exposures increased ~dose‑proportionally; ADC half‑life ~3–4 days, payload ~5 days. (oncologypro.esmo.org)

Efficacy

All‑comers, early ESMO Asia dataset (as of May 24, 2024): Among 77 response‑evaluable patients across dose levels, unconfirmed ORR (uORR) 28.6% (95% CI 18.9–40.0) and disease control rate (DCR) 83.1%. In SCLC (n=33), uORR 45.5%; responses also observed in CRPC (n=3), NSCLC (n=3), and cholangiocarcinoma (n=1). (oncologypro.esmo.org)
Expanded interim analysis (press release, presented at ESMO Asia 2024): Across evaluable patients (n=238), uORR 32.4% and DCR 82.4%. Subgroups: SCLC uORR 56.2% (n=73) overall; at 9 mg/kg, SCLC patients with prior immunotherapy but no prior topoisomerase‑I inhibitor had uORR 70.4%. CRPC uORR 28.0% (n=32), median radiographic PFS 7.2 months (data immature), 6‑month rPFS rate 94.7%. NSCLC non‑squamous uORR 22.0% (n=41), squamous uORR 16.0% (n=25). (en.dualitybiologics.com)
CRPC (ASCO 2025, press release summary): In heavily pretreated CRPC, confirmed ORR 30.8% and DCR 90.4% among 52 efficacy‑evaluable patients; 6‑month rPFS rate 69.8% among 68 evaluable patients. (prnewswire.com)

Notes: Response rates above are preliminary (often unconfirmed by independent review unless stated) and from ongoing dose‑finding/expansion cohorts; maturation of PFS/DoR data is pending. (oncologypro.esmo.org)

Safety

ESMO Asia 2024 interim (n=126 treated): Treatment‑emergent adverse events (TEAEs) in 90.5% (treatment‑related 81.0%); grade ≥3 TEAEs in 42.1% (treatment‑related 31.7%). Common any‑grade TEAEs (≥20%): nausea (46.0%; grade ≥3 2.4%), decreased neutrophil count (34.9%; 15.9%), anemia (32.5%; 7.1%), decreased platelet count (25.4%; 6.3%), decreased WBC count (23.0%; 4.8%). Dose reductions in 9.5% and discontinuations in 5.6%. (oncologypro.esmo.org)
Company ASCO 2025 summary: most frequent AEs were gastrointestinal and hematologic; discontinuation rates were low in the CRPC cohort. (Topline description only.) (prnewswire.com)

Trial status

Global Phase 1/2a, first‑in‑human, multicenter, open‑label study (DB‑1311‑O‑1001; NCT05914116); recruiting sites in the US, Australia, China, and Taiwan. Design includes dose escalation (accelerated titration then 3+3) and multiple tumor‑specific expansion cohorts. (aacrjournals.org)

Regulatory designations

FDA Fast Track designation (June 24, 2024) for advanced/unresectable or metastatic CRPC progressing after standard regimens.
FDA Orphan Drug designation (July 2024) for advanced/metastatic ESCC. (globenewswire.com)

Active trials using BNT324

Found 3 active trials using this drug:

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

Sponsor: BioNTech SE (industry) Phase: 3 Start date: April 22, 2026

TrialFetch AI summary: Randomized open-label trial for men with progressive mCRPC, ECOG 0–1, after 1–2 androgen receptor pathway inhibitors and no prior taxane/cytotoxic chemotherapy for mCRPC. Patients receive BNT324/DB-1311, a B7-H3–targeted antibody-drug conjugate carrying a topoisomerase I inhibitor payload, versus standard docetaxel plus prednisone/prednisolone while continuing castration therapy.

ClinicalTrials.gov ID: NCT07365995

A Phase Ib/II, Multi-site, Open-label, Two-part Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Recommended Combination Dose of BNT324 With BNT327 in Participants With Advanced Lung Cancer

Sponsor: BioNTech SE (industry) Phase: 1/2 Start date: May 2, 2025

TrialFetch AI summary: Adults with unresectable, advanced, or metastatic NSCLC or SCLC—including both treatment-naïve and previously treated patients—are eligible for this trial evaluating BNT324, a B7-H3-targeted antibody-drug conjugate, in combination with BNT327, a bispecific antibody targeting PD-L1 and VEGF-A. Separate cohorts include NSCLC with and without actionable oncogenic alterations and both first- and later-line treatment settings.

ClinicalTrials.gov ID: NCT06892548

A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1311 in Subjects With Advanced/Metastatic Solid Tumors

Sponsor: DualityBio Inc. (industry) Phase: 1/2 Start date: Aug. 17, 2023

TrialFetch AI summary: This trial enrolls adults with advanced or metastatic solid tumors—including SCLC, NSCLC, ESCC, CRPC, melanoma, HCC, cervical cancer, HNSCC, and select rare cancers—who have progressed after or are intolerant to standard therapies. Patients receive DB-1311, an anti-B7-H3 antibody-drug conjugate linked to a topoisomerase I inhibitor, administered intravenously every 3 weeks.

ClinicalTrials.gov ID: NCT05914116