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

• ClinicalTrials.gov Identifier: NCT05262530
• Recruitment Status: Recruiting
• First Posted: March 2, 2022
• Last Update Posted: February 23, 2023
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Biological: BNT142	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 288 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: First-in-human, Open-label, Multicenter, Phase I/IIa, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety and Preliminary Efficacy of BNT142 in Patients With CLDN6-positive Advanced Solid Tumors
• Actual Study Start Date: March 28, 2022
• Estimated Primary Completion Date: October 2025
• Estimated Study Completion Date: April 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: BNT142	Biological: BNT142; Intravenous bolus/infusion

Outcome Measures

Primary Outcome Measures :

1. Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to trial treatment [ Time Frame: From first dose to 60 days after the last dose of BNT142 ]
2. Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs [ Time Frame: From first dose to 60 days after the last dose of BNT142 ]
3. Part 1: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period (Cycle 1, i.e., 21 days after the first dose) during the dose escalation [ Time Frame: assessed during the first cycle (21 days) in each cohort ]
4. Part 2: Objective response rate (ORR) [ Time Frame: at least 48 months subsequent to first dose, are lost to follow-up, or have died ]
   ORR is defined as the proportion of patients in whom a 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.

Secondary Outcome Measures :

1. Part 1: PK parameter: Area under the concentration-time curve in the dosing interval (AUC) [ Time Frame: pre-dose until 60 days after last dose ]
2. Part 1: PK parameter: Clearance (CL) [ Time Frame: pre-dose until 60 days after last dose ]
3. Part 1: PK parameter: Volume of distribution (Vd) [ Time Frame: pre-dose until 60 days after last dose ]
4. Part 1: PK parameter: Maximum observed concentration (Cmax) [ Time Frame: pre-dose until 60 days after last dose ]
5. Part 1: PK parameter: Time to maximum observed concentration (Tmax) [ Time Frame: pre-dose until 60 days after last dose ]
6. Part 1: PK parameter: Concentration prior to next dose (Ctrough) [ Time Frame: pre-dose until 60 days after last dose ]
7. Part 1: PK parameter: Minimum observed concentration (Cmin) [ Time Frame: pre-dose until 60 days after last dose ]
8. Part 1: PK parameter: Elimination half-life (t½) [ Time Frame: pre-dose until 60 days after last dose ]
9. Disease control rate (DCR) [ Time Frame: at least 48 months subsequent to first dose, are lost to follow-up, or have died ]
   DCR is defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1 [and per GCIG criteria for ovarian cancer patients], SD assessed at least 6 weeks after first dose) as best overall response.
10. Duration of response (DOR) [ Time Frame: at least 48 months subsequent to first dose, are lost to follow-up, or have died ]
    DOR is defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST 1.1) or death from any cause, whichever occurs first.
11. Part 1: ORR [ Time Frame: at least 48 months subsequent to first dose, are lost to follow-up, or have died ]
    ORR (Part 1 only; this is a primary endpoint for Part 2) is defined as the proportion of patients in whom a CR or PR, per RECIST 1.1, is the best overall response.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

For Part 1 and 2:

• Histological or cytological documentation of a solid tumor that is metastatic or unresectable via a pathology report.
• CLDN6-positive tumor sample as assessed by central testing using a validated immunohistochemistry (IHC) assay in formalin-fixed paraffin-embedded (FFPE) 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 non-small cell lung cancer (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 (NOS) tumors not included in the eligible tumor types, including rare tumors and cancers of unknown primary, 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 Food and Drug Administration (FDA), American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO) or local guidelines used at the site), and failed at least first line standard of care (SOC) therapy prior to enrollment.

Key Exclusion Criteria:

• Radiotherapy, chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of trial treatment; nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment.
• 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 monoclonal antibody.
• Side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 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;
• Have no neurological symptoms (excluding Grade ≤2 neuropathy);
• Have stable brain metastasis on the computer tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent form (ICF); and
• Are not undergoing acute corticosteroid therapy or steroid taper.
• Notes: Patients with central nervous system (CNS) symptoms should undergo a CT scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases are allowed, unless imminent fracture with cord compression is anticipated.
• Pregnant or breastfeeding or planning to get pregnant within 6 months of the last dose of BNT142.

Contacts and Locations

Contacts

Contact: BioNTech clinical trials patient information; +49 6131 9084 ext 0; patients@biontech.de

Locations

United States, California

Cedars-Sinai Medical Center; Not yet recruiting

Los Angeles, California, United States, 90048

United States, Indiana

Indiana University School of Medicine; Not yet recruiting

Indianapolis, Indiana, United States, 46202

United States, Maryland

University of Maryland Medical Center; Not yet recruiting

Baltimore, Maryland, United States, 21201

United States, New York

Memorial Sloan Kettering Cancer Center; Not yet recruiting

New York, New York, United States, 10065

United States, North Carolina

Duke University Medical Center; Not yet recruiting

Durham, North Carolina, United States, 27705

United States, Pennsylvania

University of Pennsylvania; Not yet recruiting

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

South Texas Accelerated Research Therapeutics (START) - San Antonio; Recruiting

San Antonio, Texas, United States, 78229

United States, Virginia

NEXT Virginia; Recruiting

Fairfax, Virginia, United States, 22031

Singapore

National University Cancer Institute - National University Hospital; Not yet recruiting

Singapore, Singapore, 119074

Spain

Hospital Universitario Vall D'Hebron; Recruiting

Barcelona, Spain, 08035

MD Anderson Cancer Center; Recruiting

Madrid, Spain, 28033

START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz; Recruiting

Madrid, Spain, 28040

START Madrid CIOCC Hospital Universitario HM Sanchinarro; Recruiting

Madrid, Spain, 28050

Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos; Not yet recruiting

Malaga, Spain, 29010

Sponsors and Collaborators

BioNTech SE

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

More Information

• Responsible Party: BioNTech SE
• ClinicalTrials.gov Identifier: NCT05262530
• Other Study ID Numbers: BNT142-01; 2021-005481-18 ( EudraCT Number )
• First Posted: March 2, 2022
• Last Update Posted: February 23, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by BioNTech SE:

CLDN6-positive solid tumors

Additional relevant MeSH terms:

Neoplasms