Solid Tumor
Conditions
Keywords
CLDN6-positive 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.
Interventions
BIOLOGICALBNT142
Intravenous bolus/infusion
Sponsors
BioNTech SE
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: NOTE: Other protocol defined Inclusion/
Exclusion criteria
may apply. For Part 1 and 2: * Histological or cytological documentation of a malignant solid tumor (via a pathology report) that is metastatic or unresectable. * CLDN6-positive tumor sample as assessed by central laboratory testing using a validated immunohistochemistry 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 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 guidelines) and cancers of unknown primary, not included in the pre-defined eligible tumor types (the last three 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 United States Food and Drug Administration \[FDA\], American Society of Clinical Oncology, European Society for Medical Oncology or local guidelines used at the site), and failed at least first line standard of care therapy prior to enrollment. Key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 in the dose escalation | Assessed during the DLT period, i.e., up to 5 weeks after first dose of BNT142 | — |
| Part 2: Objective response rate (ORR) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Part 1: ORR | 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. |
| Disease control rate (DCR) | 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) | 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. |
Countries
Singapore, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORBioNTech Responsible Person
BioNTech SE
Outcome results
None listed