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: April 3, 2024
• Sponsor: BioNTech SE
• Information provided by (Responsible Party): BioNTech SE

Tracking Information

• First Submitted Date: February 21, 2022
• First Posted Date: March 2, 2022
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: March 28, 2022
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2024)

• Occurrence of treatment emergent adverse events (TEAEs) including Grade ≥3, serious, or fatal TEAEs by causal relationship to study treatment [ Time Frame: From first dose to 60 days after the last dose of BNT142 ]
• 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 ]
• 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 ]
• Part 2: Objective response rate (ORR) [ Time Frame: up to 36 months after last patient last dose ]
  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.

Original Primary Outcome Measures (submitted: February 21, 2022)

• 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 ]
• 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 ]
• 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 ]
• 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.

Current Secondary Outcome Measures (submitted: April 2, 2024)

• 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 ]
• Part 1: PK parameter: Clearance (CL) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Volume of distribution (Vd) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Maximum observed concentration (Cmax) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Time to maximum observed concentration (Tmax) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Concentration prior to next dose (Ctrough) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Minimum observed concentration (Cmin) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Elimination half-life (t½) [ Time Frame: pre-dose until 60 days after last dose ]
• Disease control rate (DCR) [ Time Frame: up to 36 months after last patient last dose ]
  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.
• Duration of response (DOR) [ Time Frame: up to 36 months after last patient last dose ]
  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.
• Part 1: ORR [ Time Frame: up to 36 months after last patient last dose ]
  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.

Original Secondary Outcome Measures (submitted: February 21, 2022)

• 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 ]
• Part 1: PK parameter: Clearance (CL) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Volume of distribution (Vd) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Maximum observed concentration (Cmax) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Time to maximum observed concentration (Tmax) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Concentration prior to next dose (Ctrough) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Minimum observed concentration (Cmin) [ Time Frame: pre-dose until 60 days after last dose ]
• Part 1: PK parameter: Elimination half-life (t½) [ Time Frame: pre-dose until 60 days after last dose ]
• 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.
• 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.
• Anti-drug antibodies (ADAs) response [ Time Frame: pre-dose until 60 days after last dose ]
  ADAs response assessed with BNT142-encoded protein anti-RiboMab02.1, and anti-polyethylene glycol (PEG) lipid antibodies.
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Preliminary Efficacy Trial of BNT142 in Patients With CLDN6-positive Solid Tumors
• 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
• 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

Biological: BNT142

Intravenous bolus/infusion

Study Arms

Experimental: BNT142

Intervention: Biological: BNT142

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 2, 2024): 330
• Original Estimated Enrollment (submitted: February 21, 2022): 216
• Estimated Study Completion Date: April 2026
• Estimated Primary Completion Date: October 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Singapore, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05262530
• Other Study ID Numbers: BNT142-01; 2021-005481-18 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: BioNTech SE
• Original Responsible Party: Same as current
• Current Study Sponsor: BioNTech SE
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: BioNTech Responsible Person; BioNTech SE

• PRS Account: BioNTech SE
• Verification Date: April 2024