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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: BNT142


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BNT142<br> | Biological: BNT142<br>* Intravenous bolus/infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to trial 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 (Cycle 1, i.e., 21 days after the first dose) during the dose escalation |  | assessed during the first cycle (21 days) in each cohort | 
| Part 2: Objective response rate (ORR) | 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. | at least 48 months subsequent to first dose, are lost to follow-up, or have died | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Part 1: PK parameter: Concentration prior to next dose (Ctrough) |  | pre-dose until 60 days after last dose | 
| Part 1: PK parameter: Minimum observed concentration (Cmin) |  | pre-dose until 60 days after last dose | 
| Part 1: PK parameter: Elimination half-life (t½) |  | pre-dose until 60 days after last dose | 
| 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. | at least 48 months subsequent to first dose, are lost to follow-up, or have died | 
| 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. | at least 48 months subsequent to first dose, are lost to follow-up, or have died | 
| Part 1: ORR | 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. | at least 48 months subsequent to first dose, are lost to follow-up, or have died | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLDN6-positive solid tumors