Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy Trial of BNT141

• Status: Recruiting
• Trial end date: 2024-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This trial is an open-label, multi-site, Phase I/IIa dose escalation, safety, and pharmacokinetic (PK) trial of BNT141 followed by expansion cohorts in patients with CLDN18.2-positive tumors.

The trial design consists of three parts:

Part 1A is a dose escalation of BNT141 as monotherapy in patients with unresectable or metastatic Claudin 18.2 (CLDN18.2)-positive gastric cancer, gastroesophageal junction (GEJ) and esophageal cancer of the adenocarcinoma subtype, colorectal cancer, pancreatic cancer, biliary tract cancers, and mucinous ovarian cancer, for which there is no available standard therapy likely to confer clinical benefit, or the patient is not a candidate for such available therapy. The dose of BNT141 will be escalated until the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of BNT141 as monotherapy are defined.

Part 1B is a dose escalation of BNT141 in combination with nab-paclitaxel and gemcitabine in patients with advanced unresectable or metastatic CLDN18.2-positive pancreatic adenocarcinoma or cholangiocarcinoma who are eligible for treatment with nab-paclitaxel and gemcitabine. Part 1B intends to define the MTD and/or RP2D of the combination.

Part 2 with adaptive design elements will be added at a later stage.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: BioNTech SE
• Treatments: Gemcitabine; Paclitaxel

Criteria

Key inclusion criteria:

For all Parts:

• Histological or cytological documentation of a solid tumor that is metastatic or unresectable 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. 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 unresectable or metastatic gastric cancer, gastroesophageal junction (GEJ) and esophageal cancer of the adenocarcinoma subtype, pancreatic cancer, biliary tract cancers, mucinous ovarian cancers and colorectal cancer, 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 (SOC) therapy prior to enrolment. Measurable or evaluable disease per RECIST 1.1.

For Part 1B: Patients with advanced unresectable or metastatic pancreatic adenocarcinoma or cholangiocarcinoma who are eligible for treatment with nabpaclitaxel 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; 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 intravenous [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).

• 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 NCI-CTCAE v.5.0 Grade ≤ 1, with the exception of alopecia, anorexia, vitiligo, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy. Anorexia, hyperthyroidism, hypothyroidism, and peripheral neuropathy 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 (CT) or magnet resonance imaging (MRI) scan within 4 weeks before signing the informed consent form (ICF).

• Not undergoing acute corticosteroid therapy or steroid taper.