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

Overview

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.

Interventions

• Biological BNT317 DL1
  Intravenous infusion
• Biological BNT317 DL2
  Intravenous infusion
• Biological BNT317 DL3
  Intravenous infusion
• Biological BNT317 DL4
  Intravenous infusion
• Biological BNT317 DL5 (intermediate)
  Intravenous infusion
• Biological BNT317 DL6 (intermediate)
  Intravenous infusion
• Biological BNT317 DL7 (additional)
  Intravenous infusion

Primary outcome measures

• Occurrence of DLTs [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) [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 [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 outcome measures (9)

• 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

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• Norton Cancer Institute PARENT — Louisville
• START Midwest — Grand Rapids
• Carolina BioOncology Institute, LLC — Huntersville
• Rhode Island Hospital — East Providence
• MUSC Hollings Cancer Center — Charleston
• Mary Crowley Cancer Research — Dallas
• South Texas Accelerated Research Therapeutics (START), LLC — San Antonio

Australia · 4 centers

• Tasman Oncology Research Ltd — Southport
• Cancer Research SA — Adelaide
• Monash Medical Centre Clayton — Clayton
• Scientia Clinical Research — Randwick

Identifiers

NCT: NCT06750185 · BNT317-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗