Bemarituzumab in FGFR2b+ Patients With Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed at Least One Prior Line of Palliative Chemotherapy

NCT06680622 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: BEMARA2024-512484-31-00
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 35

Brief Summary

The goal of this clinical trial is to evaluate if bemarituzumab in combination with different standard of care chemotherapies enhance tumor response in patients with FGFR2b-positive advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. The main questions are: How do patients respond to these treatments? How is the overall and the progression-free survival rate with these treatments? How is the disease control rate with these treatments? How long is the duration of response and disease stabilization with these treatments? How is the safety with these treatments? How is the quality of life with these treatments? Patients will be allocated to one of three possible treatment cohorts according to investigator's decision and current standard of care: Bemarituzumab with cohort 1: irinotecan cohort 2: paclitaxel plus ramucirumab cohort 3: trifluridine/tipiracil

Conditions

Metastatic Gastro-esophageal Adenocarcinoma

Keywords

BEMARA; FGFR2b; adenocarcinoma of the stomach or gastroesophageal junction

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate (ORR), defined as proportion of subjects with a complete response (CR) or partial response (PR) acc. to RECIST v1.1, for each cohort (cohort 1 - bemarituzumab plus irinotecan, cohort 2 - bemarituzumab plus paclitaxel and ramucirumab, cohort 3 - bemarituzumab plus trifluridine/tipiracil).

  from date of enrollment to date of last response acc. to RECIST v1.1 or death due to any cause, through study completion, up to 33 months

Secondary Outcomes (8)

• Progression-free survival (PFS)

  from date of enrollment to date of progression acc. to RECIST v1.1 or death due to any cause, through study completion, up to 33 months

• Overall survival (OS)

  time from date of enrollment to date of death due to any cause, through study completion, up to 33 months

• Disease control rate (DCR)

  time from date of enrollment to date of last tumor assessment acc. to RECIST 1.1 or death due to any cause, through study completion, up to 33 months

• Duration of response (DoR)

  time from response initiation (when either CR or PR is first determined) to date of progression or death to any cause, through study completion, up to 33 months

• Disease stabilization

  time from the first assessment of CR or PR or SD until the date of progression or death to any cause, through study completion, up to 33 months

Study Arms (3)

Cohort 1

EXPERIMENTAL

bemarituzumab plus SOC treatment with irinotecan

Drug: bemarituzumab, irinotecan

Cohort 2

EXPERIMENTAL

bemarituzumab plus SOC treatment with paclitaxel plus ramucirumab

Drug: bemarituzumab, paclitaxel, ramucirumab

Cohort 3

EXPERIMENTAL

bemarituzumab plus SOC treatment with trifluridine/tipiracil

Drug: bemarituzumab, trifluridine/tipiracil

Interventions

bemarituzumab, paclitaxel, ramucirumab DRUG

Cohort 2 will receive bemarituzumab plus SOC treatment with paclitaxel and ramucirumab

Cohort 2

bemarituzumab, irinotecan DRUG

Cohort 1 will receive bemarituzumab plus SOC treatment with irinotecan

Cohort 1

bemarituzumab, trifluridine/tipiracil DRUG

Cohort 3 will receive bemarituzumab plus SOC treatment with trifluridine/tipiracil

Cohort 3

Eligibility Criteria

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

You may qualify if:

• Patient provide signed informed consent form.
• Patient is ≥ 18 years at the time of given informed consent.
• Patient has been diagnosed with histologically proven advanced or metastatic adenocarcinoma of the stomach or of the gastroesophageal junction, which is not amenable to potentially curative resection. Primary tumor locations will be classified following AJCC/UICC 8th ed.
• Patient has measurable disease or non-measurable, but evaluable disease, according to RECIST v1.1
• Patient received at least one previous line of treatment, which includes a fluoropyrimidine and a platinum, in the advanced setting or the patient has been intolerable or ineligible to fluoropyrimidine and/or platinum. Neoadjuvant/adjuvant treatment is not counted unless progression occurs \<6 months after completion of the treatment. In these cases, neoadjuvant/adjuvant treatment is counted as one line of therapy.
• Note: patient allocation to cohort 3 only if patient received at least two previous lines of treatment.
• Tumor material (archival and/or fresh) is available for centrally FGFR2b testing performed by IHC.
• FGFR2b-selected population using 2+/3+ definition in ≥ 10% tumor cells.
• Patients with HER2/neu-positive tumors are eligible if they received prior HER2/neu-targeted therapy.
• Patient has an ECOG performance status ≤ 1.
• Patient has a life expectancy \> 12 weeks.
• Patient has adequate hematological, hepatic and renal function.
• Absolute number of neutrophils (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL (5.58 mmol/L), without transfusion support within 7 days before the first dose of study treatment

You may not qualify if:

• Patient received prior treatment any selective inhibitor of the FGF-FGFR pathway or participated in a study that randomized to FGFR-targeted therapy/placebo.
• Patient has known allergic / hypersensitive reactions to at least one of the treatment components
• Contraindication for standard of care (SOC) treatment regimen chosen by investigator (irinotecan, paclitaxel plus ramucirumab or trifluridine/tipiracil) according to specific product information or clinical standards
• Patient has known presence of tumors other than adenocarcinomas (e.g., leiomyosarcoma, lymphoma) or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. The sponsor decides to include patients who have received curative treatment and have been disease-free for at least 5 years.
• Patient has squamous/ adenosquamous cell carcinoma of the stomach or gastroesophageal junction.
• Patient receives simultaneous, ongoing, systemic immunotherapy, chemotherapy, hormone therapy or investigational treatment not described in the study protocol.
• Patient receives current treatment with any anti-cancer therapy or major surgery ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured.
• Patient receives simultaneous treatment with a different anti-cancer therapy (including investigational treatments) other than that provided for in the trial (excluding palliative radiotherapy for symptom control).
• Patient has known untreated or symptomatic CNS or leptomeningeal metastases. Subjects with asymptomatic CNS metastases are eligible if clinically stable for ≥ 4 weeks and require no intervention (including use of corticosteroids). Subjects with treated brain metastases are eligible provided the following criteria are met:
• Definitive therapy was completed at least 2 weeks prior to the first planned dose of trial treatment (stereotactic radiosurgery at least 7 days prior to first planned dose of study treatment)
• At least 7 days prior to first dose of trial treatment: any CNS disease is clinically stable, subject is off steroids for CNS disease (unless steroids are indicated for a reason unrelated to CNS disease), and subject is off or on stable doses of anti-epileptic drugs
• Patient has impaired cardiac function or clinically significant cardiac disease including unstable angina within 6 months before the first dose of study treatment, acute myocardial infarction \< 6 months prior to the first dose of study treatment, New York Heart Association (NYHA) class II-IV congestive heart failure, uncontrolled hypertension (defined as an average systolic blood pressure \> 160 mmHg or diastolic \> 100 mmHg despite optimal treatment, uncontrolled cardiac arrhythmias requiring antiarrhythmic therapy other than beta blockers or digoxin, active coronary artery disease or corrected QT interval (QTc) ≥ 470
• Patient has evidence of or any ongoing ophthalmological disorders.
• History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
• Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks) or are actively progressing

Sponsors & Collaborators

• Amgen: collaborator
• Johannes Gutenberg University Mainz: collaborator
• Technical University of Munich: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (35)

Uniklinik RWTH Aachen

Aachen, 52074, Germany

Location

Klinikum St. Marien

Amberg, Germany

Location

Universitätsklinikum Augsburg

Augsburg, Germany

Location

Helios Klinikum Bad Saarow

Bad Saarow, Germany

Location

Klinikum Neukölln Vivantes Netzwerk für Gesundheit GmbH Klinlinik für Innere Medizin - Hämatologie und Onkologie

Berlin, 12351, Germany

Location

Charité - Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie (CVK)

Berlin, 13353, Germany

Location

VIVANTES Berlin Friedrichshain

Berlin, Germany

Location

Klinikum Bielefeld gem. GmbH Klinik für Hämatologie, Onkologie und Palliativmedizin

Bielefeld, Germany

Location

Klinikum Chemnitz

Chemnitz, Germany

Location

St.-Johannes-Hospital

Dortmund, 44137, Germany

Location

Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, 01307, Germany

Location

Universitätsklinikum Düsseldorf Klinik für Gastroenterologie, Hepatologie und Infektiologie Gastroonkologische Studienzentrale

Düsseldorf, 40225, Germany

Location

Kliniken Essen-Mitte

Essen, Germany

Location

Krankenhaus Nordwest GmbH Institut für Klinisch-Onkologische Forschung (IKF)

Frankfurt, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH Standort Gießen Medizinische Klinik IV; Organonkologie Studienzentrale

Giessen, 35392, Germany

Location

Universität Göttingen

Göttingen, Germany

Location

Onkodoc Gütersloh

Gütersloh, 33332, Germany

Location

Hämatologisch-Onkologische Praxis Eppendorf (hope) Norddeutsches Studienzentrum für Innovative Onkologie

Hamburg, 20249, Germany

Location

MH Hannover

Hanover, Germany

Location

Universitätsklinikum Heidelberg Nationales Centrum für Tumorerkrankungen (NCT Heidelberg)

Heidelberg, 69120, Germany

Location

St. Anna Hospital Herne

Herne, 44649, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

Medizinisches Versorgungszentrum Landshut

Landshut, Germany

Location

Universitäres Krebszentrum Leipzig (UCCL)

Leipzig, 04103, Germany

Location

Klinikum Magdeburg

Magdeburg, Germany

Location

Universitätsmedizin Mainz I. Medizinische Klinik und Poliklinik

Mainz, 55131, Germany

Location

Klinikum rechts der Isar der technischen Univeristät München Medizinische Klinik und Poliklinik III Hämatologie und Onkologie

München, 81675, Germany

Location

Klinikum der Universität München Med. Klinik und Poliklinik III AG Onkologie

München, Germany

Location

Klinikum München-Bogenhausen

München, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93042, Germany

Location

Krankenhaus Barmherzige Brüder Regensburg Klinik für Onkologie und Hämatologie

Regensburg, 93049, Germany

Location

Kreiskliniken Reutlingen gGmbH Klinikum am Steinenberg Reutlingen/Medizinische Klinik I

Reutlingen, 72746, Germany

Location

HELIOS Kliniken Schwerin

Schwerin, Germany

Location

Klinikum Wolfsburg Medizinische Klinik II

Wolfsburg, 38440, Germany

Location

MeSH Terms

Interventions

bemarituzumab; Paclitaxel; Ramucirumab; Irinotecan; Trifluridine; tipiracil

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Sylvie Lorenzen, Prof. Dr.

  Klinikum München rechts der Isar der Technischen Universität München

  PRINCIPAL INVESTIGATOR

• Salah Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2024
• First Posted: November 8, 2024
• Study Start: March 3, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (35)