E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CLDN18.2-positive solid tumors |
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E.1.1.1 | Medical condition in easily understood language |
CLDN18.2-positive solid tumors |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10017758 |
E.1.2 | Term | Gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066354 |
E.1.2 | Term | Adenocarcinoma of the gastroesophageal junction |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015332 |
E.1.2 | Term | Esophageal adenocarcinoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004676 |
E.1.2 | Term | Biliary tract disease |
E.1.2 | System Organ Class | 100000004871 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008593 |
E.1.2 | Term | Cholangiocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063916 |
E.1.2 | Term | Metastatic gastric cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of BNT141 at different dose levels
To identify the maximum tolerated dose (MTD) or maximally administered dose (MAD) /recommended Phase II dose (RP2D) of BNT141 based on the occurrence of dose-limiting toxicities (DLTs) using the following definitions: • The MTD will be defined as the highest tolerated dose, where less than one-third of the patients experience a DLT. • The MAD is defined as the highest dose administered, where all dose levels were tolerated during dose escalation. • The RP2D will be defined based on integrated evaluation of safety, tolerability, clinical benefit, pharmacokinetic (PK), and pharmacodynamic (PD) data, for all dose levels tested.
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E.2.2 | Secondary objectives of the trial |
To characterize the PK profile of the BNT141-encoded protein RiboMab01.
To evaluate the anti-tumor activity of BNT141 according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 SOC therapy prior to enrolment. Measurable or evaluable disease per RECIST 1.1. 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. • 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.
• For Part 2 (Expansion): − Cohort 1 – Pancreatic adenocarcinoma: pancreatic adenocarcinoma eligible for treatment with nab-paclitaxel and gemcitabine. Measurable disease per RECIST 1.1. − Cohort 2 – Cholangiocarcinoma: cholangiocarcinoma eligible for treatment with nab-paclitaxel and gemcitabine. Measurable disease per RECIST 1.1.
For complete list of inclusion criteria, please refer to the protocol. |
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E.4 | Principal exclusion criteria |
• 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 intravenous [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 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 AEs (NCICTCAE) v.5 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 (CT) or magnet resonance imaging (MRI) scan within 4 weeks before signing the informed consent form (ICF). − Not undergoing acute corticosteroid therapy or steroid taper.
For complete list of exclusion criteria, please refer to the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
* Occurrence of treatment-emergent adverse events (TEAEs) within a patient including Grade ≥ 3, serious, fatal TEAE by relationship. * Occurrence of dose reductions and discontinuation of BNT141 due to TEAEs. * Occurrence of DLTs within a patient during the DLT evaluation period.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Refer to protocol for timepoints of evaluation |
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E.5.2 | Secondary end point(s) |
* PK parameters including but not limited to area-under-theconcentration-time curve (AUC), clearance (CL), volume of distribution (Vd), maximum concentration (Cmax), time to Cmax (tmax)measured concentration at the end of a dosing interval [taken directly before next administration] (Ctrough), and half-life (t½). * Objective response rate (ORR) is defined as the proportion of patients in whom a complete response (CR) or partial response ([PR], per RECIST 1.1) is confirmed as best overall response. * Disease control rate (DCR) is defined as the proportion 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. * Duration of response (DOR) is 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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Refer to protocol for timepoints of evaluation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, Biomarker Analysis, Immunogenicity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Different dose of the same product |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 11 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Netherlands |
Spain |
Germany |
Denmark |
Portugal |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial is considered completed when all patients: * have had at least 12 months survival follow up OR * are lost to follow up OR * have withdrawn consent OR * have died OR * the sponsor discontinues the trial.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |