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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor
• 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)

• Registration Number: NCT06750185
• Lead Sponsor: BioNTech SE

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, or investigator decision.

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 dose levels may be evaluated based on the available safety, antitumor activity, PK, and pharmacodynamic (PD) data.

Study Timeline

• Study First Submitted: 2024-12-12
• Study First Submitted QC: 2024-12-19
• Study First Posted: 2024-12-27
• Study Start: 2025-01-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-04
• Last Update Posted: 2025-02-06
• Primary Completion: 2028-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

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 trial 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.
  • Broad-spectrum intravenous antibiotics therapy within 2 weeks prior to the first dose of IMP.
  • Any investigational product within 4 weeks before the first dose of IMP in this trial or ongoing participation in the active treatment phase of another interventional clinical trial.
  • Systemic cytotoxic chemotherapy, immunotherapy within 4 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 a single area of 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 trial.
  • Participants with known leptomeningeal metastases.

• Have uncontrolled hypertension or poorly controlled diabetes.

• 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. Patients 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BNT317 DL1	BNT317 DL1	BNT317 monotherapy
BNT317 DL2	BNT317 DL2	BNT317 monotherapy
BNT317 DL3	BNT317 DL3	BNT317 monotherapy
BNT317 DL4	BNT317 DL4	BNT317 monotherapy
BNT317 DL5 (optional, intermediate)	BNT317 DL5 (intermediate)	BNT317 monotherapy
BNT317 DL6 (optional, intermediate)	BNT317 DL6 (intermediate)	BNT317 monotherapy
BNT317 DL7 (optional, additional)	BNT317 DL7 (additional)	BNT317 monotherapy

Primary Outcome Measures

Name	Time	Method
Occurrence of DLTs	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)	Per dose group. During the DLT observation period.
Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs)	from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated	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
Occurrence of dose interruption or discontinuation of study treatment due to TEAEs	from first IMP administration up to 14 days after the last dose of IMP	Per dose group.
MTD or the recommended phase two dose (RP2D) of BNT317	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

Name	Time	Method
Objective Response Rate (ORR)	from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated	Per dose group. Defined as the proportion of participants in whom a complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\]) is observed as best overall response.
Duration of Response (DOR)	from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated	Per dose group. Defined defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST 1.1) or death from any cause, whichever occurs first.
Disease Control Rate (DCR)	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	Per dose group. Defined as the proportion of participants in whom a CR, PR or stable disease (per RECIST 1.1) is observed as best overall response.
PK assessment: The maximum (peak) serum concentration (Cmax)	from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)	Per dose group. If data permits.
PK assessment: Time to reach maximum (peak) serum concentration (Tmax)	from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)	Per dose group. If data permits.
PK assessment: Elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time-curve (t1/2)	from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)	Per dose group. If data permits.
PK assessment: The area under the curve (AUC) from time zero to infinity (mass × time × volume-1) (AUCinf)	from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)	Per dose group. If data permits.
PK assessment: The AUC from time zero to last quantifiable measurement (AUClast)	from pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)	Per dose group. If data permits.
Change from baseline in serum levels of anti-drug antibody (ADA)	from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated	Per dose group. If data permits.

Trial Locations

Locations (4)

START Midwest; 🇺🇸 Grand Rapids, Michigan, United States

Carolina BioOncology Institute, LLC; 🇺🇸 Huntsville, North Carolina, United States

Mary Crowley Cancer Research; 🇺🇸 Dallas, Texas, United States

South Texas Accelerated Research Therapeutics (START), LLC; 🇺🇸 San Antonio, Texas, United States