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

NCT04683939 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: BNT141-012022-001843-25
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Solid Tumor; Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma; Pancreatic Cancer; Biliary Tract Cancer; Cholangiocarcinoma; Metastatic Cancer

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; Precision oncology; Solid tumors; mRNA

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• RiboMab PK Parameter - Area Under the Concentration Time Curve (AUC)

  First treatment cycle (From first dose up to 21 days after first dose)

• RiboMab PK Parameter - Clearance

  First treatment cycle (From first dose up to 21 days after first dose)

• RiboMab PK Parameter - Volume of Distribution at Steady State (Vss)

  First treatment cycle (From first dose up to 21 days after first dose)

• RiboMab PK Parameter - Maximum Serum Drug Concentration (Cmax)

  First treatment cycle (From first dose up to 21 days after first dose)

• RiboMab PK Parameter - Time to Reach Cmax (Tmax)

  First treatment cycle (From first dose up to 21 days after first dose)

Study Arms (3)

Part 1A - BNT141 monotherapy escalation

EXPERIMENTAL

Administration once every three weeks (Q3W)

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.

Drug: BNT141; Drug: Nab-paclitaxel; Drug: Gemcitabine

Part 2 - predefined expansion cohorts

EXPERIMENTAL

BNT141 in combination with nab-paclitaxel and gemcitabine

Drug: BNT141; Drug: Nab-paclitaxel; Drug: Gemcitabine

Interventions

BNT141 DRUG

Intravenous (IV)

Part 1A - BNT141 monotherapy escalation; Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine; Part 2 - predefined expansion cohorts

Nab-paclitaxel DRUG

IV

Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine; Part 2 - predefined expansion cohorts

Gemcitabine DRUG

IV

Part 1B - BNT141 in combination with nab-paclitaxel and gemcitabine; Part 2 - predefined expansion cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (7)

City of Hope

Duarte, California, 91010, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

START

San Antonio, Texas, 78229, United States

Location

University of Montreal - Centre Hospitalier de l´Université de Montréal

Montreal, H2X3E4, Canada

Location

St. Michaels Hospital

Toronto, M5B1W8, Canada

Location

Princess Margaret Cancer Centre - University Health Network

Toronto, M5G1X5, Canada

Location

Related Publications (1)

• 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.

  PMID: 37860278 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma Of Esophagus; Pancreatic Neoplasms; Biliary Tract Neoplasms; Cholangiocarcinoma; Neoplasm Metastasis; Esophageal Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Biliary Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

+49 6131 9084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2020
• First Posted: December 24, 2020
• Study Start: January 18, 2022
• Primary Completion: July 24, 2023
• Study Completion: July 24, 2023
• Last Updated: October 2, 2024
• Results First Posted: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (3)