Solid TumorPhase 1/2NCT04683939
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
A Phase 1/2 study testing BNT141, Nab-paclitaxel and Gemcitabine in people with Solid Tumor and Gastric Cancer, run by BioNTech SE at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma
- What is being tested?
- BNT141, Nab-paclitaxel and Gemcitabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 18 Jan 2022to 24 Jul 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 standard of care therapy prior to enrolment. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Eligible tumor types are gastric cancer, 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.
- 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.
Who cannot join
- 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 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) 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 Adverse Events (NCI CTCAE) v.5.0 Grade ≤ 1, with the exception of anorexia, fatigue, hyperthyroidism, hypothyroidism, and peripheral neuropathy, which must have recovered to ≤ Grade 2. Alopecia of any grade is allowed.
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- 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 or magnet resonance imaging scan within 4 weeks before signing the informed consent form.
- Not undergoing acute corticosteroid therapy or steroid taper.
- Additional inclusion and exclusion criteria did apply (please refer to the clinical study protocol for detailed information).
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States4 sites
City of Hope
Duarte, California, 91010
MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Oncology
San Antonio, Texas, 78229
START
San Antonio, Texas, 78229
Canada3 sites
University of Montreal - Centre Hospitalier de l´Université de Montréal
Montreal, H2X3E4
St. Michaels Hospital
Toronto, M5B1W8
Princess Margaret Cancer Centre - University Health Network
Toronto, M5G1X5
About this study
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
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.
Read the 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
- Solid Tumor, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Pancreatic Cancer, Biliary Tract Cancer
- Being tested
- BNT141, Nab-paclitaxel, Gemcitabine
- Keywords
- CLDN18.2-positive solid tumors, Gastric cancer, Gastric adenocarcinoma, Gastroesophageal junction adenocarcinoma, Esophageal adenocarcinoma, Esophageal cancer, Pancreatic cancer, Pancreatic ductal adenocarcinoma, Biliary tract cancers, Cholangiocarcinoma, Mucinous ovarian cancers, Metastatic, Treatment, Therapy, Targeted immunotherapy, Metastatic cancer, Ribomab, CLDN18.2-positive tumors, Biomarker, Precision medicine
- Medical subject headings
- Stomach Neoplasms, Adenocarcinoma Of Esophagus, Pancreatic Neoplasms, Biliary Tract Neoplasms, Cholangiocarcinoma, Neoplasm Metastasis, Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BNT141Drug
Intravenous (IV)
Nab-paclitaxelDrug
IV
GemcitabineDrug
IV
| Study group | Role | What they receive |
|---|---|---|
| Part 1A - BNT141 monotherapy escalation | Experimental | Administration once every three weeks (Q3W) Receives: Drug: BNT141 |
| Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine | Experimental | BNT141 was planned to be administered Q3W. Nab-paclitaxel and gemcitabine was planned to be administered on three days of each 28-day cycle. Receives: Drug: BNT141; Drug: Nab-paclitaxel; Drug: Gemcitabine |
| Part 2 - predefined expansion cohorts | Experimental | BNT141 in combination with nab-paclitaxel and gemcitabine Receives: Drug: BNT141; Drug: Nab-paclitaxel; Drug: Gemcitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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.
Measured: First treatment cycle (From first dose up to 21 days after first dose)
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study start18 Jan 2022
- Primary completion24 Jul 2023
- Study completion24 Jul 2023
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by BioNTech SEThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech SE
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- BioNTech Responsible Person, Study director, BioNTech SE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04683939
- Sponsor's protocol ID
- BNT141-01
- Other IDs
- 2022-001843-25
- Status last verified
- Sep 2024
- First submitted
- 21 Dec 2020
- Last updated
- 2 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bahr-Mahmud H, Ellinghaus U, Stadler CR, Fischer L, Lindemann C, Chaturvedi A, Diekmann J, Woll S, Biermann I, Hebich B, Scharf C, Siefke M, Roth AS, Rao M, Brettschneider K, Ewen EM, Sahin U, Tureci O. Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody. Oncoimmunology. 2023 Oct 16;12(1):2255041. doi: 10.1080/2162402X.2023.2255041. eCollection 2023.
PubMed 37860278
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04683939
- Acronym / sponsor ID
- BNT141-01
- Conditions
- Solid Tumor, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Pancreatic Cancer, Biliary Tract Cancer
- Keywords
- CLDN18.2-positive solid tumors, Gastric cancer, Gastric adenocarcinoma, Gastroesophageal junction adenocarcinoma, Esophageal adenocarcinoma, Esophageal cancer, Pancreatic cancer, Pancreatic ductal adenocarcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 13 participants (actual)
- Lead sponsor
- BioNTech SEIndustry (pharma, biotech, devices)
- Study start
- 18 Jan 2022 (actual)
- Primary completion
- 24 Jul 2023 (actual)
- Study completion
- 24 Jul 2023 (actual)
- First posted
- 24 Dec 2020 (actual)
- Results
- Posted 2 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1A - BNT141 monotherapy escalation | Experimental | Drug: BNT141Administration once every three weeks (Q3W) |
| Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine | Experimental | Drug: BNT141, Drug: Nab-paclitaxel, Drug: GemcitabineBNT141 was planned to be administered Q3W. Nab-paclitaxel and gemcitabine was planned to be administered on three days of each 28-day cycle. |
| Part 2 - predefined expansion cohorts | Experimental | Drug: BNT141, Drug: Nab-paclitaxel, Drug: GemcitabineBNT141 in combination with nab-paclitaxel and gemcitabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
- 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 standard of care therapy prior to enrolment. Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Eligible tumor types are gastric cancer, 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.
- 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.
Key exclusion criteria (12 listed)
- 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 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) 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BNT141Intravenous (IV) | Drug | Part 1A - BNT141 monotherapy escalation, Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine, Part 2 - predefined expansion cohorts |
| Nab-paclitaxelIV | Drug | Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine, Part 2 - predefined expansion cohorts |
| GemcitabineIV | Drug | Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine, Part 2 - predefined expansion cohorts |
Primary outcome
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship
Time frame: From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.
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
Occurrence of Dose Reductions and Discontinuation of BNT141 Due to TEAEs
Time frame: From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.
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
Occurrence of Dose-limiting Toxicities (DLTs) Within a Patient During the DLT Evaluation Period
Time frame: First treatment cycle (From first dose up to 21 days after first dose)
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.
10 secondary outcomes
RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC)
Time frame: First treatment cycle (From first dose up to 21 days after first dose)
RiboMab PK Parameter - Clearance
Time frame: First treatment cycle (From first dose up to 21 days after first dose)
RiboMab PK Parameter - Volume of Distribution at Steady State (Vss)
Time frame: First treatment cycle (From first dose up to 21 days after first dose)
RiboMab PK Parameter - Maximum Serum Drug Concentration (Cmax)
Time frame: First treatment cycle (From first dose up to 21 days after first dose)
RiboMab PK Parameter - Time to Reach Cmax (Tmax)
Time frame: 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)
Time frame: Before start of Cycle 3 (plasma sample taken directly before BNT141 Cycle 3 administration)
RiboMab PK Parameter - Half-time (t½)
Time frame: First treatment cycle (From first dose up to 21 days after first dose)
Objective Response Rate (ORR)
Time frame: 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)
Time frame: 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)
Time frame: From start of first dose of BNT141 until end of trial or start of a new anti-cancer therapy, up to 30 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37860278Bahr-Mahmud H, Ellinghaus U, Stadler CR, Fischer L, Lindemann C, Chaturvedi A, Diekmann J, Woll S, Biermann I, Hebich B, Scharf C, Siefke M, Roth AS, Rao M, Brettschneider K, Ewen EM, Sahin U, Tureci O. Preclinical characterization of an mRNA-encoded anti-Claudin 18.2 antibody. Oncoimmunology. 2023 Oct 16;12(1):2255041. doi: 10.1080/2162402X.2023.2255041. eCollection 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
BioNTech Responsible Person study director
BioNTech SE
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BNT141, Nab-paclitaxel and Gemcitabine in people with Solid Tumor and Gastric Cancer, run by BioNTech SE at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Treatment-emergent Adverse Events (TEAEs) Within a Patient Including Grade ≥ 3, Serious, Fatal TEAE by Relationship (time frame: From start of BNT141 treatment until the second Safety Follow-up Visit (60 ± 7 days after last dose), up to 30 weeks.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04683939, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2024.