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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
73
Intravenous bolus/infusion
University of Maryland Medical Center
Baltimore, Maryland, United States
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 in the dose escalation
Time frame: Assessed during the DLT period, i.e., up to 5 weeks after first dose of BNT142
Part 2: Objective response rate (ORR)
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.
Time frame: Up to 36 months after last patient last dose
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
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Duke University Medical Center
Durham, North Carolina, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
South Texas Accelerated Research Therapeutics (START) - San Antonio
San Antonio, Texas, United States
NEXT Virginia
Fairfax, Virginia, United States
National University Cancer Institute - National University Hospital
Singapore, Singapore
HM Nou Delfos General Hospital
Barcelona, Spain
Hospital Universitario Vall D'Hebron
Barcelona, Spain
MD Anderson Cancer Center
Madrid, Spain
...and 8 more locations
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
Part 1: ORR
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.
Time frame: Up to 36 months after last patient 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.
Time frame: Up to 36 months after last patient last dose
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.
Time frame: Up to 36 months after last patient last dose