A Phase I, First-in-human, Open-label, Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BNT317 in Patients With Advanced Solid Tumors
Summary
This is a first-in-human (FIH), open-label, multiple-site, dose escalation study which will evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of increasing doses of BNT317 in participants with advanced solid tumors.
Detailed description
Participants will be assigned to one of four dose levels of BNT317. One treatment cycle contains one treatment. Participants may receive investigational medicinal product (IMP) for up to 2 years or until they experience disease progression, unacceptable toxicities, withdrawal of consent, study discontinuation or investigator decision. The total duration of the study for a singe participant may be up to 2 years, plus follow-up until the last participant has completed 1 year of survival follow-up (excluding screening). In the dose escalation phase, an accelerated titration design for Dose Level 1 (DL1) and a Bayesian Optimal Interval (BOIN) design for DL2 to DL4 will be used to evaluate dose limiting toxicities (DLTs) and determine the maximum tolerated dose (MTD). Additional dosing schedules and/or intermediate or higher dose levels may be evaluated based on the available safety, antitumor activity, PK, and pharmacodynamic (PD) data.
Arms & interventions
- BiologicalBNT317 DL1
Intravenous infusion
- BiologicalBNT317 DL2
Intravenous infusion
- BiologicalBNT317 DL3
Intravenous infusion
- BiologicalBNT317 DL4
Intravenous infusion
- BiologicalBNT317 DL5 (intermediate)
Intravenous infusion
- BiologicalBNT317 DL6 (intermediate)
Intravenous infusion
- BiologicalBNT317 DL7 (additional)
Intravenous infusion
Outcome measures
Primary
Occurrence of DLTs
Per dose group. During the DLT observation period.
Time frame: up to 28 days post IMP administration on Day 1 of Cycle 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days)
Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs)
Per dose group. Assessed according to (US National Cancer Institute) Common Terminology Criteria for Adverse Events version 5.0, including Grade ≥3, serious, fatal TEAE by relationship.
Time frame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Occurrence of dose interruption or discontinuation of study treatment due to TEAEs
Per dose group.
Time frame: from first IMP administration up to 14 days after the last dose of IMP
MTD or the recommended phase two dose (RP2D) of BNT317
Time frame: For MTD, up to 28 days post IMP administration on Cycle 1 Day 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days) or, for RP2D, up to 100 days
Secondary
Objective Response Rate (ORR)
Time frame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Duration of Response (DOR)
Time frame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Disease Control Rate (DCR)
Time frame: from at least 6 weeks after the first IMP dose up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
PK assessment: The maximum (peak) serum concentration (Cmax) of BNT317
Time frame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
PK assessment: Time to reach maximum (peak) serum concentration (Tmax) of BNT317
Time frame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
PK assessment: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time-curve (t1/2) of BNT317
Time frame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
PK assessment: The area under the curve (AUC) from time zero to infinity (mass × time × volume-1) (AUCinf) of BNT317
Time frame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
PK assessment: The AUC from time zero to the end of the dosing period of BNT317
Time frame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
The proportion of participants who are anti-drug antibody (ADA) positive against BNT317
Time frame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Eligibility criteria
Study locations (7)
Norton Cancer Institute PARENT
Louisville, Kentucky, 40202
START Midwest
Grand Rapids, Michigan, 49546
Carolina BioOncology Institute, LLC
Huntersville, North Carolina, 28078
Rhode Island Hospital
East Providence, Rhode Island, 02903
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
Mary Crowley Cancer Research
Dallas, Texas, 75230
South Texas Accelerated Research Therapeutics (START), LLC
San Antonio, Texas, 78229