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Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer (FORTITUDE-102)

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ClinicalTrials.gov Identifier: NCT05111626
Recruitment Status : Recruiting
First Posted : November 8, 2021
Last Update Posted : May 25, 2022
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:

The main objective of Part 1 is to evaluate the safety and tolerability of bemarituzumab plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) and nivolumab.

The main objective Part 2 is to compare efficacy of bemarituzumab plus mFOLFOX6 and nivolumab to placebo plus mFOLFOX6 and nivolumab as assessed by overall survival.


Condition or disease Intervention/treatment Phase
Gastric Cancer Gastroesophageal Junction Adenocarcinoma Drug: Bemarituzumab Drug: Nivolumab Drug: mFOLFOX6 Other: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 702 participants
Allocation: N/A
Intervention Model: Parallel Assignment
Intervention Model Description:

This is a Phase 1b/3 study:

  • Phase 1b (Part 1) is a single-arm open-label study, which will enroll about 20 participants
  • Phase 3 (Part 2) is a randomized double-blind 2-arm study, which will enroll 682 participants
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b/3 Study of Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab Alone in Subjects With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer With FGFR2b Overexpression
Actual Study Start Date : March 14, 2022
Estimated Primary Completion Date : May 11, 2026
Estimated Study Completion Date : May 11, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab
Participants will be administered bemarituzumab at different doses with mFOLFOX6 and nivolumab to determine the recommended phase 3 dose (RP3D) based on occurence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK).
Drug: Bemarituzumab
Bemarituzumab will be administered as intravenous (IV) infusion.
Other Name: AMG 552

Drug: Nivolumab
Nivolumab will be administered as IV infusion.

Drug: mFOLFOX6
5-fluorouracil, leucovorin, and oxaliplatin will be administered as IV infusion.

Experimental: Part 2: Bemarituzumab with mFOLFOX6 and Nivolumab
Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab.
Drug: Bemarituzumab
Bemarituzumab will be administered as intravenous (IV) infusion.
Other Name: AMG 552

Drug: Nivolumab
Nivolumab will be administered as IV infusion.

Drug: mFOLFOX6
5-fluorouracil, leucovorin, and oxaliplatin will be administered as IV infusion.

Placebo Comparator: Part 2: Placebo with mFOLFOX6 and Nivolumab
Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab.
Drug: Nivolumab
Nivolumab will be administered as IV infusion.

Drug: mFOLFOX6
5-fluorouracil, leucovorin, and oxaliplatin will be administered as IV infusion.

Other: Placebo
Placebo will be administered as IV infusion.




Primary Outcome Measures :
  1. Part 1: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [ Time Frame: 28 days ]
  2. Part 1: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 4.5 years ]
  3. Part 1: Number of Participants Who Experienced One or More Related TEAEs [ Time Frame: Up to 4.5 years ]
  4. Part 1: Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to 4.5 years ]
  5. Part 1: Number of Participants With Clinically Significant Changes in Visual Acuity [ Time Frame: Up to 4.5 years ]
  6. Part 1: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) [ Time Frame: Up to 4.5 years ]
  7. Part 1: Number of Participants With Clinically Significant Changes in Physical Examinations [ Time Frame: Up to 4.5 years ]
  8. Part 1: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: Up to 4.5 years ]
  9. Part 2: Overall Survival [ Time Frame: Up to 4.5 years ]

Secondary Outcome Measures :
  1. Part 1 & 2: Objective Response (OR) [ Time Frame: Up to 4.5 years ]
  2. Part 1 & 2: Duration of Response (DoR) [ Time Frame: Up to 4.5 years ]
  3. Part 1 & 2: Disease Control Rate (DCR) [ Time Frame: Up to 4.5 years ]
  4. Part 1 & 2: Progression Free Survival (PFS) [ Time Frame: Up to 4.5 years ]
  5. Part 1: Overall Survival [ Time Frame: Up to 4.5 years ]
  6. Part 2: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 4.5 years ]
  7. Part 2: Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to 4.5 years ]
  8. Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity [ Time Frame: Up to 4.5 years ]
  9. Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: Up to 4.5 years ]
  10. Part 1: Area Under the Concentration Time Curve (AUC) for Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
  11. Part 1 & 2: Maximum Observed Concentration (Cmax) for Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
  12. Part 1 & 2: Observed Concentration at the End of a Dose Interval (Ctrough) for Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
  13. Part 1 & 2: Number of Participants With Anti-Bemarituzumab Antibody Formation [ Time Frame: Day 1 to up to 4.5 years ]
  14. Part 2: Mean Score in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Version 3.0 (QLQ-C30) Individual Scores [ Time Frame: Up to 4.5 years ]
  15. Part 2: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Version 3.0 (QLQ-C30) Individual Scores [ Time Frame: Baseline to up to 4.5 years ]
  16. Part 2: Mean Score in Stomach Cancer Related Symptoms Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Stomach 22 (QLQ-STO22) [ Time Frame: Up to 4.5 years ]
  17. Part 2: Change From Baseline in Stomach Cancer Related Symptoms Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Stomach 22 (QLQ-STO22) [ Time Frame: Baseline to up to 4.5 years ]
  18. Part 2: Mean Score of Visual Analogue Scale (VAS) Scores as Measured by EuroQol 5-dimensional (EQ-5D-5L) [ Time Frame: Up to 4.5 years ]
  19. Part 2: Change From Baseline of Visual Analogue Scale (VAS) Scores as Measured by EuroQol 5-dimensional (EQ-5D-5L) [ Time Frame: Baseline to up to 4.5 years ]
  20. Part 2: Time to Deterioration in Stomach Cancer Related Symptoms Measured by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Stomach 22 (QLQ-STO22) [ Time Frame: Day 1 to up to 4.5 years ]
  21. Part 2: Time to Deterioration in Health-Related Quality of Life (HRQoL) Scores [ Time Frame: Day 1 to up to 4.5 years ]
  22. Part 2: Time to Deterioration in Physical Function Scores [ Time Frame: Day 1 to up to 4.5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria Part 1:

  • Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
  • Participant has no contraindications to mFOLFOX6 chemotherapy or nivolumab
  • Adequate organ function as follows:

    • Absolute neutrophil count ≥ 1.5 x 10^9/L
    • Platelet count ≥ 100 x 10^9/L
    • Hemoglobin ≥ 9 g/dL without red blood cell (RBC) transfusion within 7 days prior to the first dose of study treatment
    • Aspartate aminotransaminase (AST) and Alanine aminotransaminase (ALT) <3 x upper limit of normal (ULN) (or < 5 x ULN if liver involvement)
    • Total bilirubin <1.5 x ULN (or < 2 x ULN if liver involvement or Gilbert's disease)
    • Calculated or measured creatinine clearance (CrCl) of ≥ 50 mL/minute calculated using the formula of Cockcroft and Gault
    • International Normalized Ratio (INR) or prothrombin time (PT) < 1.5 × ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment

Additional Inclusion Criteria Part 2:

  • No prior treatment for metastatic or unresectable disease except for a maximum of 1 dose of mFOLFOX6 with or without nivolumab. Prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed, provided it has been completed more than 6 months prior to the first dose of study treatment
  • Fibroblast growth factor receptor 2b (FGFR2b) overexpression positive as determined by centrally performed immunohistochemistry (IHC) testing

Exclusion Criteria:

  • Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
  • Known positive human epidermal growth factor receptor 2 (HER2) status
  • Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease
  • Peripheral sensory neuropathy grade 2 or higher
  • Clinically significant cardiac disease
  • Other malignancy within the last 2 years (exceptions for definitively treated disease)
  • Chronic or systemic ophthalmologic disorders
  • Major surgery or other investigational study within 28 days prior to randomization
  • Palliative radiotherapy within 14 days prior to randomization
  • Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
  • Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05111626


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, Arizona
Mayo Clinic - Arizona Recruiting
Phoenix, Arizona, United States, 85054
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
University of California Los Angeles Bowyer Hematology-Oncology Clinic Recruiting
Los Angeles, California, United States, 90095
Innovative Clinical Research Institute Recruiting
Whittier, California, United States, 90603
United States, Florida
Mayo Clinic Florida Recruiting
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10022
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology - Austin Midtown Recruiting
Austin, Texas, United States, 78705
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
United States, Washington
Northwest Cancer Specialists - Vancouver Recruiting
Vancouver, Washington, United States, 98684
Japan
National Cancer Center Hospital East Recruiting
Kashiwa-shi, Chiba, Japan, 277-8577
The Cancer Institute Hospital of Japanese Foundation for Cancer Research Recruiting
Koto-ku, Tokyo, Japan, 135-8550
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT05111626    
Other Study ID Numbers: 20210098
First Posted: November 8, 2021    Key Record Dates
Last Update Posted: May 25, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Bemarituzumab
AMG 552
5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6)
Nivolumab
Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
FGFR2b Overexpression
Additional relevant MeSH terms:
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Adenocarcinoma
Stomach Neoplasms
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Nivolumab
Bemarituzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action