Dose Escalation Trial of BNT152+153 in Patients With Cancer

NCT04710043 | Completed Phase 1 FDA Drug

• 3 other identifiers: BNT152-01C2021-005599-202023-509508-13-00
• Study Type: interventional
• Target: 86
• Locations: 2 countries
• Sites: 7

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.

Conditions

Solid Tumor

Keywords

BioNTech SE; Solid Tumors; Metastatic; Unresectable; Advanced solid malignancies

Outcome Measures

Primary Outcomes (4)

• Occurrence of treatment-emergent adverse events (TEAEs) including Grade ≥ 3, serious, fatal TEAE by causal relationship to trial treatment

  TEAEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.

  up to 24 months

• Occurrence of dose reduction and discontinuation of investigational medicinal product within a patient due to TEAE

  up to 24 months

• Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period - BNT152

  21 days

• Occurrence of DLTs during the DLT evaluation period - BNT153

  21 days

Secondary Outcomes (3)

• Objective response rate (ORR)

  up to 24 months

• Disease control rate (DCR)

  up to 24 months

• Duration of response (DOR)

  up to 24 months

Study Arms (6)

Part 1 group A BNT153

EXPERIMENTAL

Monotherapy dose escalation.

Drug: BNT153

Part 1 group B BNT152

EXPERIMENTAL

Monotherapy dose escalation.

Drug: BNT152

Part 2A - BNT152+153

EXPERIMENTAL

Escalating dose levels up to RP2D

Drug: BNT152; Drug: BNT153

Part 2B - BNT152+153

EXPERIMENTAL

Escalating dose levels up to RP2D

Drug: BNT152; Drug: BNT153

Part 2C - BNT152+153

EXPERIMENTAL

Escalating dose levels up to RP2D

Drug: BNT152; Drug: BNT153

Part 2 - BNT152+153 - biomarker cohort

EXPERIMENTAL

Drug: BNT152; Drug: BNT153

Interventions

BNT152 DRUG

intravenous

Part 1 group B BNT152; Part 2 - BNT152+153 - biomarker cohort; Part 2A - BNT152+153; Part 2B - BNT152+153; Part 2C - BNT152+153

BNT153 DRUG

intravenous

Part 1 group A BNT153; Part 2 - BNT152+153 - biomarker cohort; Part 2A - BNT152+153; Part 2B - BNT152+153; Part 2C - BNT152+153

Eligibility Criteria

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

You may qualify if:

• 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 RECIST1.1.
• 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 1.
• 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
• Absolute neutrophil count ≥ 1.5 × 10\^9/L (patient may not use granulocyte-colony stimulating factor or granulocyte-macrophage colony stimulating factor to achieve these WBC and absolute neutrophil count levels)
• Platelet count ≥ 100 × 10\^9/L
• Hemoglobin ≥ 9.0 g/dL
• Adequate hepatic function at screening as determined by:
• Total bilirubin ≤ 1.5 mg/dL (or ≤ 2.0 mg/dL for patients with known Gilbert's syndrome or liver metastasis)

You may not qualify if:

• 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 ≤ 1. Note: peripheral neuropathy Grade ≤ 2 is allowed; alopecia of any grade is allowed.
• Medical conditions:
• Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain metastases may be eligible if they:
• had radiotherapy, surgery or stereotactic surgery for the brain metastases,
• have no neurological symptoms (excluding Grade ≤ 2 neuropathy),
• have stable brain metastasis on the computerized tomography (CT) or magnetic resonance imaging (MRI) scan within 4 weeks before signing the informed consent,
• are not undergoing acute corticosteroid therapy or steroid taper. Notes: Patients with central nervous system symptoms should undergo a CT-scan or MRI of the brain to exclude new or progressive brain metastases. Spinal bone metastases are allowed, unless imminent fracture with cord compression is anticipated.
• Has a history of a cerebrovascular accident or had a transient ischemic attack less than 6 months before signing the ICF.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (7)

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, 60611, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Masaryk Memorial Cancer Institute

Brno, 65653, Czechia

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 12, 2021
• First Posted: January 14, 2021
• Study Start: June 8, 2021
• Primary Completion: September 10, 2025
• Study Completion: September 10, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); CZ (1)