Claudin 6 (CLDN6)-positive advanced solid tumors MedDRA version: 21.0 Level: LLT Classification code 10043302 Term: Testicular cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lun
Conditions
Interventions
Product Name: BNT142
Product Code: BNT142
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Not applicable
Current Sponsor code: RB_RMAB02.1 (mix of RBP021.1 and RBP022.1)
Other descri
Sponsors
BioNTech SE
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Parts 1 and 2: To assess the safety and tolerability of BNT142 at all dose levels tested. Part 1: To identify the maximum administered dose/maximum tolerated dose/recommended Phase II dose (MAD/MTD/RP2D) of BNT142 based on the occurrence of dose-limiting toxicities (DLTs) using the following definitions: • The MTD is defined as the highest tolerated dose where less than 1/3 patients experience a DLT. The MAD is defined as the highest dose administered, where all dose levels were tolerated during dose escalation. • The RP2D will be defined based on integrated evaluation of safety, tolerability, clinical benefit, PK and PD data from all dose levels tested. Part 2: To evaluate the anti-tumor activity of BNT142 according to RECIST 1.1 and for ovarian cancer patients according to definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and cancer antigen 125 (CA 125) agreed by the Gynecological Cancer Intergroup (GCIG).;Secondary Objective: Parts 1 and 2: To characterize the PK profile of the BNT142-encoded protein RiboMab02.1. Parts 1 and 2: To evaluate the anti-tumor activity of BNT142 according to RECIST 1.1, and for ovarian cancer patients according to definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and cancer antigen 125 (CA 125) agreed by the Gynecological Cancer Intergroup (GCIG). Parts 1 and 2: To evaluate the immunogenicity of BNT142;Primary end point(s): Parts 1 and 2: • Occurrence of treatment emergent adverse events (TEAEs) including Grade =3, serious, or fatal TEAEs by causal relationship to trial treatment. • Occurrence of dose reductions and discontinuation of BNT142 due to TEAEs. Part 1: • Occurrence of DLTs during the DLT evaluation period (Cycle 1, i.e., 21 days after the first dose) during the dose escalation. Part 2: • Objective response rate (ORR) is defined as the proportion of patients in whom a complete response (CR) or partial resp | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Parts 1 and 2: • PK parameters including but not limited to AUC, CL and Vd, Cmax, tmax, Ctrough, Cmin, and t½. • 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. • Disease control rate (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) 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 assessed with BNT142-encoded protein anti-RiboMab02.1, and anti-polyethylene glycol (PEG) lipid antibodies.;Timepoint(s) of evaluation of this end point: During the treatment phase and primary follow up period (refer to the schedule of trial procedures in the protocol for further details). | — |
Countries
Spain, United States
Contacts
Public ContactClinical Trials Information
BioNTech SE
Outcome results
None listed