CLDN18.2-positive solid tumors / malignant tumor
Conditions
Interventions
The trial design consists of three parts:
• Part 1A is a dose escalation of BNT141 as monotherapy in patients with
unresectable or metastatic CLDN18.2-positive solid tumors for which there is no
avail
Sponsors
BioNTech SE
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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 SOC therapy prior to enrolment. Measurable or evaluable disease per RECIST 1.1. Eligible tumor types are gastric cancer, gastroesophageal junction (GEJ) and esophageal adenocarcinoma, pancreatic, biliary tract (cholangiocarcinoma and gallbladder cancer), and mucinous ovarian cancers. Additionally, patients with specific tumors (including colorectal cancer, non-smallcell 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. • For Part 2 (Expansion): * Cohort 1 - Pancreatic adenocarcinoma: pancreatic adenocarcinoma eligible for treatment with nab-paclitaxel and gemcitabine. Measurable disease per RECIST 1.1. * Cohort 2 - Cholangiocarcinoma: cholangiocarcinoma eligible for treatment with nab-paclitaxel and gemcitabine. Measurable disease per RECIST 1.1. (Page 5 of the protocol)
Exclusion criteria
Exclusion criteria: Patients who meet at least one of the following exclusion criteria will not be eligible for trial entry: • 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 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 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 AEs (NCICTCAE) v.5 Grade
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of treatment-emergent adverse events (TEAEs) within a patient including Grade >= 3, serious, fatal TEAE by relationship. Occurrence of dose reductions and discontinuation of BNT141 due to TEAEs. Occurrence of DLTs within a patient during the DLT evaluation period | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters including but not limited to area-under-theconcentration- time curve (AUC), clearance (CL), volume of distribution (Vd), maximum concentration (Cmax), time to Cmax (tmax), measured concentration at the end of a dosing interval [taken directly before next administration] (Ctrough), and half-life (t*). Objective response rate (ORR) is defined as the proportion of patients in whom a complete response (CR) or partial response ([PR], per RECIST 1.1) is confirmed as best overall response. Disease control rate (DCR) is defined as the proportion of patients in whom a CR or PR or SD (per RECIST 1.1, SD assessed at least 6 weeks after first dose) is observed as best overall response. • Duration of response (DOR) is defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST 1.1) or death from any cause, whichever occurs first. Progression-free survival (PFS) is defined as the time from first dose of BNT141 to first objective tumor progression (progressive disease per RECIST 1.1), or death from any cause, whichever occurs first. • Overall survival (OS) is defined as the time from first dose of BNT141 to death from any cause. Correlation of CLDN18.2 expression level with clinical outcomes. Evaluation of PD biomarkers compared to baseline. Anti-drug antibodies [ADAs] response. Evaluate pre-treatment lipid status and potential influence on BNT141 response. | — |
Countries
Netherlands
Outcome results
None listed