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

NCT06750185 | Recruiting Phase 1 FDA Drug

• 1 other identifier: BNT317-01
• Study Type: interventional
• Target: 248
• Locations: 2 countries
• Sites: 11

Brief Summary

This is a first-in-human (FIH), open-label, multi-site study which will evaluate the safety, efficacy, tolerability, pharmacokinetics (PK), and immunogenicity of increasing doses of BNT317 in participants with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

Malignant solid tumors; Immunotherapy; Standard of care (SoC) treatment; Clear cell renal cell carcinoma (ccRCC); Human epidermal growth factor receptor 2 (HER2) negative; Gastric cancer (GGC); Gastroesophageal junction cancer (GEJC); Non-small cell lung cancer (NSCLC); Actionable genomic alteration (AGA)- negative

Outcome Measures

Primary Outcomes (4)

• Part A - Occurrence of DLTs

  Per dose group. During the DLT observation period.

  Up to 28 days after initiating BNT317 administration on Day 1 of Cycle 1 or the day before Cycle 3 Day 1, whichever comes earlier (each cycle is 14 days)

• All parts - Occurrence of treatment-emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related adverse events (TRAEs), treatment-related Grade ≥3 TEAEs, and treatment-related SAEs

  Per dose group.

  From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

• All parts - Occurrence of dose interruption, reductions, and discontinuation of BNT317 due to TEAEs

  Per dose group.

  From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

• Parts B1, B2 & B3: Objective Response Rate (ORR)

  Per dose group. Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.

  From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

Secondary Outcomes (10)

• Part A - ORR

  From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

• All parts - Duration of Response

  From the first dose of BNT317 up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

• All parts - Disease Control Rate

  From at least 6 weeks (±7 days) after the first BNT317 dose up to 100 days after last dose of IMP or until a new anticancer therapy is initiated

• All Parts - PK assessment: The maximum (peak) serum concentration (Cmax) of BNT317

  From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)

• All parts - PK assessment: Time to reach maximum (peak) serum concentration (Tmax) of BNT317

  From pre-dose Cycle 1 to pre-dose Cycle 4 (each cycle is 14 days)

Study Arms (11)

Part A - BNT317 DL1

EXPERIMENTAL

BNT317 monotherapy

Biological: BNT317 DL1

Part A - BNT317 DL2

EXPERIMENTAL

BNT317 monotherapy

Biological: BNT317 DL2

Part A - BNT317 DL3

EXPERIMENTAL

BNT317 monotherapy

Biological: BNT317 DL3

Part A - BNT317 DL4

EXPERIMENTAL

BNT317 monotherapy

Biological: BNT317 DL4

Part A - BNT317 DL5

EXPERIMENTAL

BNT317 monotherapy

Biological: BNT317 DL5

Part A - BNT317 DL6 (optional)

EXPERIMENTAL

BNT317 monotherapy

Biological: BNT317 DL6

Part B1 - BNT317 selected DLA

EXPERIMENTAL

BNT317 monotherapy, DL as selected from Part A.

Biological: BNT317 selected DLA

Part B1 - BNT317 selected DLB

EXPERIMENTAL

BNT317 monotherapy, DL as selected from Part A.

Biological: BNT317 selected DLB

Part B2 - BNT317 selected DLA plus SoC chemotherapy 1

EXPERIMENTAL

BNT317 combination therapy, DL as selected from Part A.

Biological: BNT317 selected DLA; Drug: SoC chemotherapy 1

Part B2 - BNT317 selected DLB plus SoC chemotherapy 1

EXPERIMENTAL

BNT317 combination therapy, DL as selected from Part A.

Biological: BNT317 selected DLB; Drug: SoC chemotherapy 1

Part B3 - BNT317 selected DLB plus SoC chemotherapy 2

EXPERIMENTAL

BNT317 combination therapy, DL as selected from Parts B1 and B2.

Biological: BNT317 selected DLB; Drug: SoC chemotherapy 2

Interventions

BNT317 DL1 BIOLOGICAL

Intravenous infusion

Part A - BNT317 DL1

BNT317 DL2 BIOLOGICAL

Intravenous infusion

Part A - BNT317 DL2

BNT317 DL3 BIOLOGICAL

Intravenous infusion

Part A - BNT317 DL3

BNT317 DL5 BIOLOGICAL

Intravenous infusion

Part A - BNT317 DL5

BNT317 DL6 BIOLOGICAL

Intravenous infusion

Part A - BNT317 DL6 (optional)

BNT317 selected DLA BIOLOGICAL

Intravenous infusion

Part B1 - BNT317 selected DLA; Part B2 - BNT317 selected DLA plus SoC chemotherapy 1

BNT317 selected DLB BIOLOGICAL

Intravenous infusion

Part B1 - BNT317 selected DLB; Part B2 - BNT317 selected DLB plus SoC chemotherapy 1; Part B3 - BNT317 selected DLB plus SoC chemotherapy 2

SoC chemotherapy 1 DRUG

Intravenous infusion

Part B2 - BNT317 selected DLA plus SoC chemotherapy 1; Part B2 - BNT317 selected DLB plus SoC chemotherapy 1

SoC chemotherapy 2 DRUG

Intravenous infusion

Part B3 - BNT317 selected DLB plus SoC chemotherapy 2

BNT317 DL4 BIOLOGICAL

Intravenous infusion

Part A - BNT317 DL4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 v1.1. 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, as defined in the protocol.
• Have had an adequate treatment washout period before randomization/enrollment, as defined in the protocol.
• Part B1 only: Histologically confirmed diagnosis of locally advanced, unresectable (not amenable to curative surgery or radiation therapy) or metastatic clear cell RCC (including those with sarcomatoid features).
• Part B1 2L subgroup only: Had disease progression during or after one line of prior anticancer therapy for recurrent/metastatic disease which must have included immune checkpoint inhibitor and/or tyrosine kinase inhibitor (TKI).
• Part B1 3L+ subgroup only: Had disease progression during or after two or more lines of prior anticancer therapy for recurrent/metastatic disease defined as the following:
• a. Prior treatment should also contain one or two of the following treatments:
• One line of immune checkpoint inhibitor.
• At least one line of a TKI.
• Part B2 only: Undergoing SoC treatment or is willing to start SoC treatment for 2L+ HER2-negative GC/GEJC in accordance with the product label and local treatment guidelines.
• Part B2 only: Histologically and/or cytologically documented metastatic adenocarcinoma and squamous carcinoma of GC/GEJC. (Note: Esophageal squamous cell carcinoma is excluded).
• Part B2 2L subgroup only: Had disease progression during or after one prior line of anticancer therapy for recurrent/metastatic disease which must have included a fluoropyrimidine analogue and a platinum agent with or without programmed death (PD)-1/ PD-ligand 1 (PD-L1). The total of cytotoxic containing regimens must be limited to maximum of 1 line for the recurrent/metastatic setting.
• Part B2 3L+ subgroup only: Had disease progression during or after two or more lines of prior anticancer therapy for recurrent/metastatic disease defined as the following:
• Prior treatment must include one line of treatment containing a fluoropyrimidine analogue and a platinum agent, unless the participant is not a candidate in the opinion of the treating physician.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (11)

Norton Cancer Institute PARENT

Louisville, Kentucky, 40202, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

ACTIVE NOT RECRUITING

Carolina BioOncology Institute, LLC

Huntersville, North Carolina, 28078, United States

RECRUITING

Rhode Island Hospital

East Providence, Rhode Island, 02903, United States

RECRUITING

MUSC Hollings Cancer Center

Charleston, South Carolina, 29425, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

RECRUITING

South Texas Accelerated Research Therapeutics (START), LLC

San Antonio, Texas, 78229, United States

ACTIVE NOT RECRUITING

Tasman Oncology Research Ltd

Southport, Queensland, 4215, Australia

ACTIVE NOT RECRUITING

Cancer Research SA

Adelaide, 5000, Australia

ACTIVE NOT RECRUITING

Monash Medical Centre Clayton

Clayton, 3168, Australia

ACTIVE NOT RECRUITING

Scientia Clinical Research

Randwick, 2031, Australia

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Stomach Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Central Study Contacts

BioNTech clinical trials patient information

CONTACT

+49 6131 9084; patients@biontech.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 27, 2024
• Study Start: January 13, 2025
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2031
• Last Updated: September 9, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); AU (4)