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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05262530
• Other study ID #: BNT142-01
• Secondary ID: 2021-005481-18
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 28, 2022
• Est. completion date: April 2026

Study information

• Verified date: May 2024
• Source: BioNTech SE
• Contact: BioNTech clinical trials patient information
• Phone: +49 6131 9084
• Email: patients[@]biontech.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Part 1 (Dose escalation) of this study is a first-in-human (FIH), open-label, dose escalation safety and PK study of BNT142 in patients with advanced/metastatic CLDN6-positive solid tumors.

Part 2 (Expansion) will be a Phase IIa proof-of-concept study in up to three expansion cohorts of CLDN6 positive advanced/metastatic ovarian cancer, non-small cell lung cancer (NSCLC) of non-squamous type, and testicular cancer patients who have progressed on or after last prior treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 330
• Est. completion date: April 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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 laboratory testing using a validated immunohistochemistry (IHC) 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 (NOS) 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 [NCI] guidelines) and cancers of unknown primary, not included in the pre-defined eligible tumor types. Patients must have received all available standard therapies, including targeted therapies based on mutation status (per guidelines from the US 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 therapy prior to enrollment.

Key Exclusion Criteria:

• 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;

• 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; and

• Are not undergoing acute corticosteroid therapy or steroid taper.

• Notes: Patients with central nervous system 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Biological:
• BNT142
Intravenous bolus/infusion

Locations

Country	Name	City	State
Singapore	National Cancer Centre Singapore (recruiting only for Part 2)	Singapore
Singapore	National University Cancer Institute - National University Hospital	Singapore
Spain	HM Nou Delfos General Hospital	Barcelona
Spain	Hospital Universitario Vall D'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre - Centro de Actividades Ambulatorias	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	START Madrid CIOCC Hospital Universitario HM Sanchinarro	Madrid
Spain	START Madrid-FJD Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Virgen de la Victoria Campus Universitario de Teatinos	Malaga
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Guy's Hospital - Guy's & St Thomas' NHS Foundation Trust	London
United Kingdom	Hammersmith Hospital, Imperial College School Of Medicine - Imperial College Healthcare NHS Trust	London
United Kingdom	Sarah Cannon Research Institute (Recruiting only for Part 2)	London
United Kingdom	Nottingham University Hospitals NHS Trust - Nottingham City Hospital	Nottingham
United Kingdom	Churchill Hospital - Oxford University Hospitals NHS Foundation Trust	Oxford
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Duke University Medical Center	Durham	North Carolina
United States	NEXT Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Therapeutics (START) - San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
BioNTech SE

Countries where clinical trial is conducted

United States,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs		From first dose to 60 days after the last dose of BNT142
Primary	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		assessed during the first cycle (21 days) in each cohort
Primary	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	Part 1: PK parameter: Area under the concentration-time curve in the dosing interval (AUC)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Clearance (CL)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Volume of distribution (Vd)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Maximum observed concentration (Cmax)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Time to maximum observed concentration (Tmax)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Concentration prior to next dose (Ctrough)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Minimum observed concentration (Cmin)		pre-dose until 60 days after last dose
Secondary	Part 1: PK parameter: Elimination half-life (t½)		pre-dose until 60 days after last dose
Secondary	Disease control rate (DCR)	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.	up to 36 months after last patient last dose
Secondary	Duration of response (DOR)	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.	up to 36 months after last patient last dose
Secondary	Part 1: ORR	ORR (Part 1 only) is defined as the proportion of patients in whom a confirmed CR or PR, per RECIST 1.1, is the best overall response.	up to 36 months after last patient last dose