Phase I, First-in-human, Open-label, Dose Escalation Trial to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of BNT152+153 in Patients With Solid Tumors

BioNTech SE7 sites in 2 countries86 target enrollmentJune 8, 2021

ConditionsSolid Tumor

InterventionsBNT153 BNT152

Overview

Phase: Phase 1
Intervention: BNT153
Conditions: Solid Tumor
Sponsor: BioNTech SE
Enrollment: 86
Locations: 7
Primary Endpoint: Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥ 3, serious, fatal TEAE by causal relationship to trial treatment
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, multisite Phase I dose escalation, safety, pharmacokinetics (PK) and pharmacodynamics (PD) trial of BNT152+153 in various solid tumor indications.

The clinical trial will enroll patients with various solid tumors that are metastatic or unresectable for whom there is no available standard therapy likely to confer clinical benefit, or patients who are not candidates for such available therapy.

The trial consists of Part 1 and Part 2 with adaptive design elements:

Part 1 consists of Groups A and B.
- Group A is a BNT153 monotherapy dose escalation in patients with advanced solid malignancies until the maximal tolerated dose (MTD) is defined. If MTD is not reached, maximum administered dose (MAD) may be used for further development (or another dose as determined by the safety review committee [SRC]).
- Group B is a BNT152 monotherapy dose escalation in patients with advanced solid malignancies until the MTD or optimal biological dose (OBD; the lowest safe dose associated with optimal biological activity) is defined, whichever occurs earlier.
- Group A will be activated first while the time point for Group B activation is at sponsor's decision.
Part 2 will start after the MTD or MAD or another dose as determined by the SRC have been established for BNT153 and MTD or OBD for BNT152 in Part 1. Part 2 (Part 2A, 2B and 2C) is a dose escalation of BNT152+153 in patients with advanced solid malignancies until the recommended Phase II dose (RP2D) is defined.
Part 2 may implement a biomarker cohort if a clinical benefit is observed at one or more doses of BNT152+153 that show a clear PD effect in the peripheral blood. The Biomarker Cohort will recruit patients at selected sites.

Detailed Description

The Part 2 starts with Part 2A. Enrollment of Part 2B begins after dose level 1 in Part 2A is deemed safe by the SRC. The dose escalation in Part 2A continues as described in the protocol. The dose escalation in Part 2B continues as described in the protocol until RP2D is determined. To further investigate the effect of BNT152+153, Part 2C may be introduced upon review of the emerging data.

Registry

clinicaltrials.gov

Start Date

June 8, 2021

End Date

September 10, 2025

Last Updated

7 months ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

BioNTech SE

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed solid tumor that is metastatic (Stage IV) or unresectable and for whom there is no available standard therapy likely to confer clinical benefit, or patient who is not a candidate for such available therapy. If there is no contraindication, patients should have exhausted all standard of care therapies before entering the trial.
•Measurable disease per RECIST1.
•Male and female aged ≥ 18 years.
•Prior to any trial-related assessments or procedures, must sign an informed consent form (ICF) indicating that he or she understands the purpose and procedures required for the trial and are willing to participate in the trial.
•Eastern Cooperative Oncology Group performance status of 0 to
•Adequate coagulation function at screening as determined by:
•International normalized ratio or prothrombin time ≤ 1.5 × upper limit normal (ULN); unless on therapeutic anticoagulants with values within therapeutic window),
•Activated partial thromboplastin time ≤ 1.5 × ULN (unless on therapeutic anticoagulants with values within therapeutic window).
•Adequate hematologic function at screening as determined by:
•White blood cell count (WBC) ≥ 3 × 10\^9/L

Exclusion Criteria

•Prior and concomitant therapy:
•Use of any investigational medical product or device within 28 days before administration of first dose of trial treatment.
•Has been receiving: radiotherapy, chemotherapy, or molecularly-targeted agents or tyrosine kinase inhibitors within 2 weeks or 5 half-lives (whichever is longer) of the start of trial treatment; immunotherapy/monoclonal antibodies for systemic anticancer treatment within 3 weeks of the start of trial treatment; nitrosourea, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment.
•Ongoing participation in the active treatment phase of an interventional clinical trial.
•Receives concurrent systemic (oral or intravenous) steroid therapy \>10 mg prednisone daily or its physiological equivalent for an underlying condition.
•Has had major surgery within the 4 weeks before the first dose of trial treatment.
•Ongoing or active infection requiring intravenous treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of trial treatment.
•Has side effects of any prior therapy or procedures for any medical condition not recovered to NCI CTCAE v.5 Grade ≤
•Note: peripheral neuropathy Grade ≤ 2 is allowed; alopecia of any grade is allowed.
•Medical conditions: