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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: BNT317 DL1; Biological: BNT317 DL2; Biological: BNT317 DL3; Biological: BNT317 DL4; Biological: BNT317 DL5 (intermediate); Biological: BNT317 DL6 (intermediate); Biological: BNT317 DL7 (additional)

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.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BioNTech clinical trials patient information; Phone Number: +49 6131 9084; Email: patients@biontech.de

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Recruiting
    • Cancer Research SA
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Medical Centre Clayton
  • Randwick, Australia, 2031
    • Recruiting
    • Scientia Clinical Research
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Tasman Oncology Research Ltd
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute PARENT
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Carolina BioOncology Institute, LLC
  • Rhode Island
    • East Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • MUSC Hollings Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Cancer Research
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START), LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BNT317 DL1; BNT317 monotherapy	Biological: BNT317 DL1; Intravenous infusion
Experimental: BNT317 DL2; BNT317 monotherapy	Biological: BNT317 DL2; Intravenous infusion
Experimental: BNT317 DL3; BNT317 monotherapy	Biological: BNT317 DL3; Intravenous infusion
Experimental: BNT317 DL4; BNT317 monotherapy	Biological: BNT317 DL4; Intravenous infusion
Experimental: BNT317 DL5 (optional, intermediate); BNT317 monotherapy	Biological: BNT317 DL5 (intermediate); Intravenous infusion
Experimental: BNT317 DL6 (optional, intermediate); BNT317 monotherapy	Biological: BNT317 DL6 (intermediate); Intravenous infusion
Experimental: BNT317 DL7 (optional, additional); BNT317 monotherapy	Biological: BNT317 DL7 (additional); Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of DLTs	Per dose group. During the DLT observation period.	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 dose interruption or discontinuation of study treatment due to TEAEs	Per dose group.	from first IMP administration up to 14 days after the last dose of IMP
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
Occurrence of treatment emergent adverse events (TEAEs) and treatment related adverse events (TRAEs)	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.	from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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 v1.1]) is observed as best overall response.	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)	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.	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)	Per dose group. Defined as the proportion of participants with confirmed CR or PR or stable disease (per RECIST v1.1) is observed as best overall response.	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	Per dose group. If data permits.	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	Per dose group. If data permits.	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	Per dose group. If data permits.	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	Per dose group. If data permits.	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	Per dose group. If data permits.	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	During the study.	from first IMP administration up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): December 27, 2024

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Malignant solid tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BNT317-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No