Status:

TERMINATED

Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT141 in Patients With Unresectable or Metastatic CLDN18.2-positive Gastric, Pancreatic, Ovarian and Biliary Tract Tumors

Lead Sponsor:

BioNTech SE

Conditions:

Solid Tumor

Gastric Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

This study was planned as an open-label, multi-site, Phase I/IIa dose escalation, safety, and pharmacokinetic (PK) trial of BNT141 followed by expansion cohorts in patients with Claudin 18.2 (CLDN18.2...

Detailed Description

The study design consisted of three parts: * Part 1A was a dose escalation of BNT141 as monotherapy in patients with advanced unresectable or metastatic CLDN18.2-positive solid tumors for which there...

Eligibility Criteria

Inclusion

  • Key inclusion criteria:
  • For all Parts:
  • Metastatic or unresectable solid tumor.
  • Histological or cytological documentation of a solid tumor via a pathology report.
  • CLDN18.2-positive tumor sample defined as moderate-to-strong CLDN18.2 protein expression defined as intermediate (2+) to strong (3+) staining intensity in ≥ 50% of tumor cells as assessed by central testing using a CLIA-validated immunohistochemistry assay in formalin-fixed, paraffin-embedded (FFPE) neoplastic tissues. New biopsies and archival bio-samples are allowed. Bone biopsies are not allowed. Cytology specimens (including fine needle aspirates) will not be accepted for CLDN18.2 examination. If archival tissue samples from several points of time are available, the most recent one is preferred. Patients with a lower expression level or with CLDN18.2-negative cancers are not eligible.
  • Trial part-specific inclusion criteria:
  • For Part 1A: Patients with solid tumors, for which there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy. Patients must have received all available standard therapies and failed at least first-line standard of care therapy prior to enrolment. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Eligible tumor types are gastric cancer, GEJ and esophageal adenocarcinoma, pancreatic, biliary tract (cholangiocarcinoma and gallbladder cancer), and mucinous ovarian cancers. Additionally, patients with specific tumors (including colorectal cancer, non small-cell lung cancer, gastric subtype of endocervical adenocarcinoma) where there is scientific evidence that the CLDN18.2 could be elevated can be tested for CLDN18.2 expression.
  • For Part 1B: Patients with advanced pancreatic adenocarcinoma or cholangiocarcinoma who are eligible for treatment with nab-paclitaxel and gemcitabine. Measurable or evaluable disease per RECIST 1.1.
  • Key exclusion criteria:
  • Receiving: radiotherapy, chemotherapy, or molecularly-targeted agents within 3 weeks or 5 half-lives (whichever is longer) of the start of trial treatment; immunotherapy/monoclonal antibodies within 3 weeks of the start of trial treatment (excluding BNT141); nitrosoureas, antibody-drug conjugates, or radioactive isotopes within 6 weeks of the start of trial treatment. Palliative radiotherapy will be allowed.
  • Receives concurrent systemic (oral or IV) steroid therapy \>10 mg prednisone daily or its equivalent for an underlying condition. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted.
  • Major surgery within 4 weeks before the first dose of BNT141.
  • Prior treatment with a CLDN18.2 targeting monoclonal antibodies (mAb) other than BNT141.
  • Ongoing or active infection requiring IV treatment with anti-infective therapy that has been administered less than 2 weeks prior to the first dose of BNT141.
  • Side effects of any prior therapy or procedures for any medical condition not recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0 Grade ≤ 1, with the exception of anorexia, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to ≤ Grade 2. Alopecia of any grade is allowed.
  • Current evidence of new or growing brain or leptomeningeal metastases during screening. Patients with known brain or leptomeningeal metastases may be eligible if they have:
  • Radiotherapy, surgery or stereotactic surgery for the brain or leptomeningeal metastases.
  • No neurological symptoms (excluding Grade ≤ 2 neuropathy).
  • Stable brain or leptomeningeal disease on the computer tomography or magnet resonance imaging scan within 4 weeks before signing the informed consent form.
  • Not undergoing acute corticosteroid therapy or steroid taper.
  • Additional inclusion and exclusion criteria did apply (please refer to the clinical study protocol for detailed information).

Exclusion

    Key Trial Info

    Start Date :

    January 18 2022

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    July 24 2023

    Estimated Enrollment :

    13 Patients enrolled

    Trial Details

    Trial ID

    NCT04683939

    Start Date

    January 18 2022

    End Date

    July 24 2023

    Last Update

    October 2 2024

    Active Locations (7)

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    Page 1 of 2 (7 locations)

    1

    City of Hope

    Duarte, California, United States, 91010

    2

    MD Anderson Cancer Center

    Houston, Texas, United States, 77030

    3

    NEXT Oncology

    San Antonio, Texas, United States, 78229

    4

    START

    San Antonio, Texas, United States, 78229