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2022-01-18
2023-07-24
2023-07-24
13
NCT04683939
BioNTech SE
BioNTech SE
INTERVENTIONAL
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
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.
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.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2020-12-21 | 2024-07-18 | 2024-09-06 |
2020-12-21 | 2024-09-06 | 2024-10-02 |
2020-12-24 | 2024-10-02 | 2024-09 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Sequential
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Part 1A - BNT141 monotherapy escalation Administration once every three weeks (Q3W) | DRUG: BNT141
|
| EXPERIMENTAL: Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine BNT141 was planned to be administered Q3W. Nab-paclitaxel and gemcitabine was planned to be administered on three days of each 28-day cycle. | DRUG: BNT141
DRUG: Nab-paclitaxel
DRUG: Gemcitabine
|
| EXPERIMENTAL: Part 2 - predefined expansion cohorts BNT141 in combination with nab-paclitaxel and gemcitabine | DRUG: BNT141
DRUG: Nab-paclitaxel
DRUG: Gemcitabine
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship | All TEAEs are included, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date >60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator. Intensity of AEs was graded according to the NCI CTCAE v5.0, i.e.,: Grade 1 - Mild, Grade 2 - Moderate, Grade 3 - Severe, Grade 4 - Life-threatening consequences; urgent urgent intervention indicated, Grade 5 - Death related to AE | From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks. |
| Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs | All TEAEs are included, i.e., AEs with an onset date on or after the first dose of BNT141 (if the AE was absent before the first dose) or worsened after the first dose of BNT141 (if the AE was present before the first dose). AEs with an onset date >60 days after the last dose of BNT141 are included only if assessed as related to BNT141 by the investigator | From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks. |
| Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period | Serious AEs, non-serious Grade ≥ 3 non-hematological and hematological AEs as defined per DLT criteria and clinically significant abnormal laboratory values Grade ≥ 3 were collected and considered a DLT if assessed by the investigator to be at least possibly related to BNT141. Toxicities clearly not related to BNT141 (e.g., progressive disease, comorbidity, etc.) were not considered a DLT. The NCI CTCAE v.5.0 was used to grade the intensity of AEs. | First treatment cycle (From first dose up to 21 days after first dose) |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC) | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. AUC (0-tau), AUC (0-inf) and AUC (0-504) were estimated from serum concentration data from Cycle 1 using non-compartmental analysis. AUC (0-inf): Area under the drug concentration-time curve, from time zero to infinity. AUC (0-504): Area under the drug concentration-time curve, from time zero to 504 hours after the start of the infusion. AUC (0-tau): Area under the drug concentration-time curve, from time zero over the dosing interval at steady-state (Tau = 504 hours corresponding to 3-weeks administration) after the start of the infusion. | First treatment cycle (From first dose up to 21 days after first dose) |
| RiboMab PK Parameter - Clearance | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Clearance was estimated from serum concentration from Cycle 1 data using non-compartmental analysis. | First treatment cycle (From first dose up to 21 days after first dose) |
| RiboMab PK Parameter - Volume of Distribution at Steady State (Vss) | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Volume of distribution at steady state (Vss) was estimated as mean residence time calculated using last measured concentration (MRT inf) * CL. | First treatment cycle (From first dose up to 21 days after first dose) |
| RiboMab PK Parameter - Maximum Serum Drug Concentration (Cmax) | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Cmax was estimated from serum concentration from Cycle 1 data using non-compartmental analysis. | First treatment cycle (From first dose up to 21 days after first dose) |
| RiboMab PK Parameter - Time to Reach Cmax (Tmax) | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Tmax was estimated from serum concentration from Cycle 1 data using non-compartmental analysis. | First treatment cycle (From first dose up to 21 days after first dose) |
| RiboMab PK Parameter - Concentration at the End of a Dosing Interval (Taken Directly Before Next Administration) (Ctrough) | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. Ctrough was estimated from serum concentration from Cycle 1 data using non-compartmental analysis. Ctrough values are available for participants treated with dose level 1 and dose level 2 only. | Before start of Cycle 3 (plasma sample taken directly before BNT141 Cycle 3 administration) |
| RiboMab PK Parameter - Half-time (t½) | Intact RiboMab (full-length and fully assembled antibody) PK serum samples were collected and analyzed. T½ was estimated from serum concentration from Cycle 1 data using non-compartmental analysis. | First treatment cycle (From first dose up to 21 days after first dose) |
| Objective Response Rate (ORR) | ORR was defined as the number of patients in whom a complete response (CR) or partial response (PR), per RECIST 1.1 is confirmed as best overall response. | From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks |
| Disease Control Rate (DCR) | DCR was defined as the number of patients in whom a CR or PR or stable disease ([SD], per RECIST 1.1, SD assessed at least 6 weeks after first dose) is observed as best overall response. | From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks |
| Duration of Response (DoR) | DOR was 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. | From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
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