Safety and Preliminary Efficacy Trial of BNT142 in Patients With CLDN6-positive Solid Tumors

NCT05262530 | Terminated Phase 1 FDA Drug

• 3 other identifiers: BNT142-012021-005481-182024-512639-58-00
• Study Type: interventional
• Target: 73
• Locations: 4 countries
• Sites: 18

Brief Summary

This study is an open-label, multicenter, Phase I/IIa, dose escalation, safety, and pharmacokinetics (PK) study of BNT142 followed by expansion cohorts in patients with Claudin 6 (CLDN6)-positive advanced tumors.

Conditions

Solid Tumor

Keywords

CLDN6-positive solid tumors

Outcome Measures

Primary Outcomes (4)

• Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to study treatment

  From first dose to 60 days after the last dose of BNT142

• Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs

  From first dose to 60 days after the last dose of BNT142

• Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period in the dose escalation

  Assessed during the DLT period, i.e., up to 5 weeks after first dose of BNT142

• Part 2: Objective response rate (ORR)

  ORR is defined as the proportion of patients in whom a confirmed complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and per Gynecological Cancer Intergroup (GCIG) criteria incorporating RECIST 1.1 and cancer antigen (CA)-125 for the ovarian cancer population is the best overall response.

  Up to 36 months after last patient last dose

Secondary Outcomes (11)

• Part 1: PK parameter: Area under the concentration-time curve in the dosing interval (AUC)

  Pre-dose until 60 days after last dose

• Part 1: PK parameter: Clearance (CL)

  Pre-dose until 60 days after last dose

• Part 1: PK parameter: Volume of distribution (Vd)

  Pre-dose until 60 days after last dose

• Part 1: PK parameter: Maximum observed concentration (Cmax)

  Pre-dose until 60 days after last dose

• Part 1: PK parameter: Time to maximum observed concentration (Tmax)

  Pre-dose until 60 days after last dose

Study Arms (1)

BNT142

EXPERIMENTAL

Biological: BNT142

Interventions

BNT142 BIOLOGICAL

Intravenous bolus/infusion

BNT142

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• For Part 1 and 2:
• Histological or cytological documentation of a malignant solid tumor (via a pathology report) that is metastatic or unresectable.
• CLDN6-positive tumor sample as assessed by central laboratory testing using a validated immunohistochemistry assay in formalin-fixed paraffin-embedded neoplastic tissues or alternatively from fresh tissue if archival tissue is unavailable. If archival tissue samples from several points of time are available, the most recent one is preferred.
• Measurable disease per RECIST 1.1 (measurable per RECIST 1.1 or evaluable per GCIG criteria for ovarian tumors).
• For Part 1 (Dose escalation):
• Patients with advanced/metastatic ovarian (including fallopian tube and peritoneal), non-squamous NSCLC, endometrial, or testicular cancer, for whom there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy, or patients with not otherwise specified tumors (as confirmed by histological diagnosis), rare tumors (defined as those occurring in \<15 out of 100,000 people each year as per National Cancer Institute guidelines) and cancers of unknown primary, not included in the pre-defined eligible tumor types (the last three upon approval by the medical monitor). Patients must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the United States Food and Drug Administration \[FDA\], American Society of Clinical Oncology, European Society for Medical Oncology or local guidelines used at the site), and failed at least first line standard of care therapy prior to enrollment.
• Chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of study treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of study treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of study treatment.
• Radiotherapy in the last 6 weeks prior to the first dose of BNT142 (excluding brain radiotherapy for which 3 weeks prior to the first dose of BNT142 is allowed). Previously irradiated tumor lesions cannot be considered as target lesions or non-target lesions in this study.
• Concurrent systemic (oral or intravenous \[IV\]) steroid therapy \>10 mg prednisone daily or its equivalent for an underlying condition apart from physiologic corticosteroid replacement therapy.
• Major surgery within 4 weeks before the first dose of BNT142.
• Ongoing or active infection requiring IV treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of BNT142.
• Prior treatment with a CLDN6 targeting therapy.
• Side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events v.5 Grade ≤1, except for anorexia, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to Grade ≤2. Alopecia of any grade is allowed.
• Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain metastases may be eligible if they:
• Had radiotherapy, surgery or stereotactic surgery for the brain metastases;

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (18)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics (START) - San Antonio

San Antonio, Texas, 78229, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

National University Cancer Institute - National University Hospital

Singapore, 119074, Singapore

Location

HM Nou Delfos General Hospital

Barcelona, 08023, Spain

Location

Hospital Universitario Vall D'Hebron

Barcelona, 08035, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre - Centro de Actividades Ambulatorias

Madrid, 28041, Spain

Location

START Madrid CIOCC Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos

Málaga, 29010, Spain

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, L7 8YA, United Kingdom

Location

Hammersmith Hospital, Imperial College School Of Medicine - Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

Churchill Hospital - Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (2)

• Stadler CR, Ellinghaus U, Fischer L, Bahr-Mahmud H, Rao M, Lindemann C, Chaturvedi A, Scharf C, Biermann I, Hebich B, Malz A, Beresin G, Falck G, Hacker A, Houben A, Erdeljan M, Wolf K, Kullmann M, Chang P, Tureci O, Sahin U. Preclinical efficacy and pharmacokinetics of an RNA-encoded T cell-engaging bispecific antibody targeting human claudin 6. Sci Transl Med. 2024 May 22;16(748):eadl2720. doi: 10.1126/scitranslmed.adl2720. Epub 2024 May 22.

  PMID: 38776391 DERIVED

• Simon AG, Lyu SI, Laible M, Woll S, Tureci O, Sahin U, Alakus H, Fahrig L, Zander T, Buettner R, Bruns CJ, Schroeder W, Gebauer F, Quaas A. The tight junction protein claudin 6 is a potential target for patient-individualized treatment in esophageal and gastric adenocarcinoma and is associated with poor prognosis. J Transl Med. 2023 Aug 17;21(1):552. doi: 10.1186/s12967-023-04433-8.

  PMID: 37592303 DERIVED

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 2, 2022
• Study Start: March 22, 2022
• Primary Completion: December 22, 2025
• Study Completion: December 22, 2025
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); SG (1); ES (7); GB (4)