This is a first-in-human (FIH), open-label, multi-site study which will evaluate the safety, efficacy, tolerability, pharmacokinetics (PK), and immunogenicity of increasing doses of BNT317 in participants with advanced solid tumors.
The study will consist of four parts, Part A, Part B1, Part B2 and Part B3. Part A will be a dose escalation part to investigate the safety and tolerability of BNT317 in participants with advanced solid tumors and may enroll additional participants with advanced solid tumors to specific dose levels (DLs), based on the emerging safety, PK, and pharmacodynamic data. Part A will evaluate up to six DLs of BNT317 monotherapy. Part B will include dose optimization and dose expansion components to further investigate the safety and tolerability of BNT317 and to investigate preliminary antitumor activity, i.e.: * Part B1 will further evaluate BNT317 monotherapy in participants with second-line of therapy or higher (2L+) clear cell renal cell carcinoma (ccRCC). Participants will be randomized 1:1 into two dose groups which will evaluate two DLs (as selected from Part A). * Part B2 will further evaluate BNT317 when added to standard of care (SoC) treatment in participants with 2L+ human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC)/gastroesophageal junction cancer (GEJC). Participants will be randomized 1:1 into two dose groups which will evaluate two DLs (as selected from Part A). * Part B3 will further evaluate BNT317 when added to SoC treatment in participants with 2L+ actionable genomic alteration (AGA)-negative non-small cell lung cancer (NSCLC) at the higher of the two BNT317 dose groups being investigated in Parts B1 and B2. 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 single 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 Part A (dose escalation), an accelerated titration design for DL1 and a Bayesian Optimal Interval (BOIN) design for dose groups DL2 and above will be used to evaluate dose limiting toxicities (DLTs). Additional dosing schedules and/or intermediate or higher DLs may be evaluated based on the available safety, antitumor activity, PK, and pharmacodynamic data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
248
Intravenous infusion
Intravenous infusion
Intravenous infusion
Norton Cancer Institute PARENT
Louisville, Kentucky, United States
RECRUITINGSTART Midwest
Grand Rapids, Michigan, United States
ACTIVE_NOT_RECRUITINGPart A - Occurrence of DLTs
Per dose group. During the DLT observation period.
Time frame: Up to 28 days after initiating BNT317 administration on Day 1 of Cycle 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days)
All parts - Occurrence of treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related adverse events (TRAEs), treatment-related Grade ≥3 TEAEs, and treatment-related SAEs
Per dose group.
Time frame: From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
All parts - Occurrence of dose interruption, reductions, and discontinuation of BNT317 due to TEAEs
Per dose group.
Time frame: From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Parts B1, B2 & B3: Objective Response Rate (ORR)
Per dose group. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.
Time frame: From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Part A - ORR
Per dose group. Defined as the proportion of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response.
Time frame: From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
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Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Intravenous infusion
Carolina BioOncology Institute, LLC
Huntersville, North Carolina, United States
RECRUITINGRhode Island Hospital
East Providence, Rhode Island, United States
RECRUITINGMUSC Hollings Cancer Center
Charleston, South Carolina, United States
RECRUITINGMary Crowley Cancer Research
Dallas, Texas, United States
RECRUITINGSouth Texas Accelerated Research Therapeutics (START), LLC
San Antonio, Texas, United States
ACTIVE_NOT_RECRUITINGTasman Oncology Research Ltd
Southport, Queensland, Australia
ACTIVE_NOT_RECRUITINGCancer Research SA
Adelaide, Australia
ACTIVE_NOT_RECRUITINGMonash Medical Centre Clayton
Clayton, Australia
ACTIVE_NOT_RECRUITING...and 1 more locations
All parts - Duration of Response
Per dose group. Defined as the time from first objective response (CR or PR per RECIST v1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1) or death from any cause, whichever occurs first.
Time frame: From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
All parts - Disease Control Rate
Per dose group. Defined as the proportion of participants in whom a confirmed CR or PR or stable disease (per RECIST v1.1) is observed as best overall response per investigator's assessment.
Time frame: From at least 6 weeks (±7 days) after the first BNT317 dose up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
All Parts - PK assessment: The maximum (peak) serum concentration (Cmax) of BNT317
Per dose group. If data permits.
Time frame: From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
All parts - PK assessment: Time to reach maximum (peak) serum concentration (Tmax) of BNT317
Per dose group. If data permits.
Time frame: From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
All parts - PK assessment: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time-curve (t1/2) of BNT317
Per dose group. If data permits.
Time frame: From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
All parts - PK assessment: The area under the curve (AUC) from time zero to infinity (AUCinf) of BNT317
Per dose group. If data permits.
Time frame: From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
All parts - PK assessment: The AUC from time zero to the end of the dosing period of BNT317
Per dose group. If data permits.
Time frame: From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
All parts - Anti-drug antibody (ADA) prevalence
Per dose group. The proportion of participants who are ADA positive (either baseline or post-baseline). If data permits.
Time frame: From first dose of BNT317 up to 31 days after last dose of IMP or until a new anticancer therapy is initiated
All parts - ADA incidence
Per dose group. The proportion of participants having treatment-emergent ADA). If data permits.
Time frame: From first dose of BNT317 up to 31 days after last dose of IMP or until a new anticancer therapy is initiated