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
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|ClinicalTrials.gov Identifier: NCT04683939|
Recruitment Status : Terminated (Sponsor decision)
First Posted : December 24, 2020
Last Update Posted : October 2, 2023
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 advanced unresectable or metastatic Claudin 18.2 (CLDN18.2)-positive 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. 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. 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-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.
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.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Gastric Cancer Gastroesophageal Junction Adenocarcinoma Esophageal Adenocarcinoma Pancreatic Cancer Biliary Tract Cancer Cholangiocarcinoma Metastatic Cancer||Biological: BNT141 Drug: Nab-paclitaxel Drug: Gemcitabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/IIa, First-in-human, Open-label, Dose Escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT141 as a Monotherapy and in Combination With Other Anti-cancer Agents in Patients With CLDN18.2-positive Solid Tumors|
|Actual Study Start Date :||January 18, 2022|
|Actual Primary Completion Date :||July 24, 2023|
|Actual Study Completion Date :||July 24, 2023|
Experimental: Part 1A - BNT141 monotherapy escalation
Administration once every three weeks (Q3W)
Experimental: Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine
BNT141 will be administered once every three weeks (Q3W). Nab-paclitaxel and gemcitabine will be administered on three days of each 28-day cycle.
- Occurrence of treatment-emergent adverse events (TEAEs) within a patient including Grade ≥ 3, serious, fatal TEAE by relationship [ Time Frame: up to 36 months ]TEAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 5.0.
- Occurrence of dose reductions and discontinuation of BNT141 due to TEAEs throughout the study and up to 60 days after last subject last treatment [ Time Frame: up to 36 months ]
- Occurrence of dose-limiting toxicities (DLTs) within a patient during the DLT evaluation period [ Time Frame: assessed during the first cycle (21 days) in each cohort ]DLTs are assessed during the first cycle (21 days) in each cohort to determine maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
- BNT141 pharmacokinetic: Area under the concentration time curve (AUC) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 pharmacokinetic: Clearance (CL) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 pharmacokinetic: Volume of distribution (VD) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 pharmacokinetic: Maximum concentration of the drug (Cmax) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 pharmacokinetic: Time to maximum concentration (Tmax) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 pharmacokinetic: Concentration prior to next dose (Ctrough) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 pharmacokinetic: Elimination half-life (t half) [ Time Frame: pre-dose until 60 days after last dose ]
- BNT141 - Objective response rate (ORR) [ Time Frame: up to 36 months ]ORR is defined as the proportion of patients in whom a complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 is confirmed as best overall response.
- BNT141 - Disease control rate (DCR) [ Time Frame: up to 36 months ]DCR is defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST v 1.1, SD assessed at least 6 weeks after first dose) is observed as best overall response.
- BNT141 - Duration of response (DOR) [ Time Frame: up to 36 months ]DOR is defined as the time from first objective response (CR or PR per RECIST v 1.1) to first occurrence of objective tumor progression (progressive disease per RECIST v 1.1) or death from any cause, whichever occurs first.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04683939
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|San Antonio, Texas, United States, 78229|
|San Antonio, Texas, United States, 78229|
|University of Montreal - Centre Hospitalier de l´Université de Montréal|
|Montréal, Canada, H2X3E4|
|St. Michaels Hospital|
|Toronto, Canada, M5B 1W8|
|Princess Margaret Cancer Centre - University Health Network|
|Toronto, Canada, M5G1X5|
|Study Director:||BioNTech Responsible Person||BioNTech SE|