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NCT06750185PHASE1Recruiting

Safety and Preliminary Effectiveness of BNT317, an Investigational Therapy for Advanced Solid Tumors

BioNTech SE

Start Date

1/13/2025

Completion Date

6/1/2028

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

Age Range: 18 years to No maximum

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.

Interventions

BIOLOGICAL

BNT317 DL1

BIOLOGICAL

BNT317 DL2

BIOLOGICAL

BNT317 DL3

BIOLOGICAL

BNT317 DL4

BIOLOGICAL

BNT317 DL5 (intermediate)

BIOLOGICAL

BNT317 DL6 (intermediate)

BIOLOGICAL

BNT317 DL7 (additional)

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Conditions

Advanced Solid Tumor

Locations

Norton Cancer Institute PARENT

Louisville, Kentucky 40202

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Carolina BioOncology Institute, LLC

Huntersville, North Carolina 28078

United States

Rhode Island Hospital

East Providence, Rhode Island 02903

United States

MUSC Hollings Cancer Center

Charleston, South Carolina 29425

United States

Mary Crowley Cancer Research

Dallas, Texas 75230

United States

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas 78229

United States

Tasman Oncology Research Ltd

Southport, Queensland 4215

Australia

Cancer Research SA

Adelaide, 5000

Australia

Monash Medical Centre Clayton

Clayton, 3168

Australia

Scientia Clinical Research

Randwick, 2031

Australia