Safety and preliminary efficacy trial of BNT142 in patients with CLDN6 positive solid tumors

Phase 1

• Conditions: Claudin 6 (CLDN6)-positive advanced solid tumors; MedDRA version: 21.0Level: LLTClassification code 10043302Term: Testicular cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10014733Term: Endometrial cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10007460Term: Carcinoma of unknown primarySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065143Term: Malignant solid tumourSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-005481-18-ES
• Lead Sponsor: BioNTech SE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-02-08
• Last Update Posted: 2 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 216

Inclusion Criteria

For both parts:
• 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 IHC assay in formalin-fixed paraffin-embedded (FFPE) neoplastic tissues. FFPE tissue can be derived from fresh biopsies and archival samples. 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, 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 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 FDA, ASCO, ESMO or local guidelines used at the site), and failed at least first line SOC therapy prior to enrollment.

For Part 2 (Expansion):
• Expansion Cohort 1: CLDN6-positive ovarian cancer patients who have received at least one systemic treatment regimen for advanced/metastatic disease with radiographic disease progression on or after last prior treatment and who are not eligible for SOC therapy at the discretion of the investigator.
• Expansion Cohort 2: CLDN6-positive non-squamous NSCLC who have received at least one prior systemic treatment regimen for advanced/metastatic disease with radiographic disease progression on or after last prior treatment and who are not eligible for SOC therapy at the discretion of the investigator.
• Expansion Cohort 3: CLDN6-positive testicular cancer patients who have received at least one systemic treatment regimen for advanced/metastatic disease with radiographic disease progression on or after last prior treatment and who are not eligible for SOC therapy at the discretion of the investigator.
Note: Patients are considered as not eligible for SOC therapy if in the opinion of the investigator, e.g., there is no effective SOC therapy available, SOC is contraindicated or patient has refused SOC treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 86
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion Criteria

Patients who meet any of the following exclusion criteria will not be eligible for trial entry:
• 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, with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified