Trials / Terminated

TerminatedNCT04683939

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

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

Status: Terminated
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 13 (actual)

Sponsor: BioNTech SE · Industry
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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)-positive tumors. The sponsor decided to stop the development of BNT141 on 24 July 2023 and the study was terminated early.

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 was no available standard therapy considered to confer clinical benefit, or the patient was not a candidate for such available therapy. The dose of BNT141 was planned to be escalated until the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of BNT141 as monotherapy was defined. However, due to the early study termination, the dose of BNT141 was not fully escalated as planned per protocol (i.e., only four doses were tested, i.e., 0.15 mg/kg, 0.30 mg/kg, 0.45 mg/kg, and 0.60 mg/kg). Once the MTD was reached, up to 10 additional patients with CLDN18.2 expressing pancreatic and biliary tract cancers were planned to be enrolled at the MTD level to obtain additional data on safety, PK and pharmacodynamics (PD). Eligible tumor types were 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 could be tested for CLDN18.2 expression. * Part 1B was planned to be a dose escalation of BNT141 in combination with nab-paclitaxel and gemcitabine in patients with locally advanced unresectable or metastatic CLDN18.2-positive pancreatic adenocarcinoma or cholangiocarcinoma who were eligible for treatment with nab-paclitaxel and gemcitabine. Part 1B intended to define the MTD and/or RP2D of the combination. Once the MTD was reached, up to 10 additional patients with CLDN18.2-expressing pancreatic adenocarcinoma or cholangiocarcinoma were planned to be enrolled at the MTD level to obtain additional data on safety, PK and PD. The MTD of BNT141 in combination with nab-paclitaxel and gemcitabine in Part 1B was planned to not exceed the monotherapy BNT141 MTD determined in Part 1A. * Part 2 (Expansion) was planned to consist of two predefined expansion cohorts in patients with CLDN18.2-positive solid tumors eligible for treatment with nab-paclitaxel and gemcitabine. Part 1B and Part 2 did not proceed and no participant was enrolled in Part 1B and Part 2.

Conditions

Interventions

Type	Name	Description
DRUG	BNT141	Intravenous (IV)
DRUG	Nab-paclitaxel	IV
DRUG	Gemcitabine	IV

Timeline

Start date: 2022-01-18
Primary completion: 2023-07-24
Completion: 2023-07-24
First posted: 2020-12-24
Last updated: 2024-10-02
Results posted: 2024-10-02

Locations

7 sites across 2 countries: United States, Canada

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04683939. Inclusion in this directory is not an endorsement.