Clinical trial NCT06750185: Safety and Preliminary Effectiveness of BNT317, an Investigational Therapy for Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Malignant solid tumors
Immunotherapy
Lead sponsor: BioNTech SE
Sponsor class: INDUSTRY
First posted: 2024-12-27
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Key Inclusion Criteria:

* Have histologically or cytologically confirmed advanced tumors, who have failed standard therapy, or for whom no standard treatment option is available, or for whom standard therapy is not appropriate.
* Have at least one measurable lesion based on RECIST 1.1. Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures, etc.) are generally not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system \[CNS\] metastasis should not be considered as a measurable lesion).
* Adequate hematologic and organ function.

Key Exclusion Criteria:

* Have received any of the following therapies or drugs within the noted time intervals prior to study treatment:

  * Any prior treatment which inhibits cluster of differentiation 39 (CD39).
  * Vaccination with live attenuated vaccine(s) within 4 weeks prior to the first dose of IMP.
  * Any investigational product within 4 weeks or 5 half lives (if the half life of the other investigational product is known), whichever is longer, before the first dose of IMP in this study or ongoing participation in the active treatment phase of another interventional clinical study.
  * Systemic cytotoxic chemotherapy, immunotherapy within 3 weeks or five half-lives of the chemotherapy (whichever is shorter) prior to the first dose of IMP.
  * Radiation therapy (chest, brain or internal organs) within 4 weeks prior to the first dose of IMP.
  * Palliative radiotherapy to metastasis within 2 weeks prior to the first dose of IMP.
  * Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 2 weeks prior to the first dose of IMP. Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) is allowed.
* Have any of the following CNS metastases:

  * Untreated brain metastases that are symptomatic or large (e.g., greater than 2 cm).
  * Treated CNS metastases who are not neurologically stable or on steroids or anticonvulsants within 2 weeks before initiating IMP of this study.
  * Brain metastases treated with radiotherapy that are not confirmed stable by magnetic resonance imaging or contrast-enhanced computer tomography 4 weeks after radiotherapy.
  * Participants with known leptomeningeal metastases.
* Have uncontrolled hypertension or poorly controlled diabetes as specified in the protocol.
* Have a history of allogeneic hematopoietic stem cell transplantation or organ transplantation.
* Have a history of serious Grade ≥3 immune-related adverse events (irAEs) or irAEs that led to discontinuation of a prior immunotherapy. Participants with a history of Grade ≥3 irAEs that did not lead to discontinuation of a prior immunotherapy may be included at the discretion of the investigator. If required by the investigator, after consultation with the sponsor.
* Have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Occurrence of DLTs
timeFrame: 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)
measure: Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs)
timeFrame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
measure: Occurrence of dose interruption or discontinuation of study treatment due to TEAEs
timeFrame: from first IMP administration up to 14 days after the last dose of IMP
measure: MTD or the recommended phase two dose (RP2D) of BNT317
timeFrame: 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 outcomes:
measure: Objective Response Rate (ORR)
timeFrame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
measure: Duration of Response (DOR)
timeFrame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: PK assessment: The maximum (peak) serum concentration (Cmax) of BNT317
timeFrame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
measure: PK assessment: Time to reach maximum (peak) serum concentration (Tmax) of BNT317
timeFrame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
measure: PK assessment: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time-curve (t1/2) of BNT317
timeFrame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
measure: PK assessment: The area under the curve (AUC) from time zero to infinity (mass × time × volume-1) (AUCinf) of BNT317
timeFrame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
measure: PK assessment: The AUC from time zero to the end of the dosing period of BNT317
timeFrame: from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)
measure: The proportion of participants who are anti-drug antibody (ADA) positive against BNT317
timeFrame: from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Norton Cancer Institute PARENT
state: Kentucky
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Huntersville
country: United States
facility: Carolina BioOncology Institute, LLC
state: North Carolina
city: East Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START), LLC
state: Texas
city: Southport
country: Australia
facility: Tasman Oncology Research Ltd
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton
Study officials:
affiliation: BioNTech SE
name: BioNTech Responsible Person
role: STUDY_DIRECTOR
References: