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Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression (FORTITUDE-101)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05052801
Recruitment Status : Recruiting
First Posted : September 22, 2021
Last Update Posted : February 2, 2023
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE September 13, 2021
First Posted Date  ICMJE September 22, 2021
Last Update Posted Date February 2, 2023
Actual Study Start Date  ICMJE March 7, 2022
Estimated Primary Completion Date August 18, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2022)
Overall Survival [ Time Frame: Up to approximately 3.5 years ]
Overall survival in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
Original Primary Outcome Measures  ICMJE
 (submitted: September 13, 2021)
Overall Survival (OS) [ Time Frame: Up to approximately 3.5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2023)
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 3.5 years ]
    PFS in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 3.5 years ]
    ORR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to approximately 3.5 years ]
    Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests after first dose will be recorded as TEAEs.
  • Overall Survival [ Time Frame: Up to approximately 3.5 years ]
    Overall survival in all randomized participants
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 3.5 years ]
    PFS in all randomized participants
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 3.5 years ]
    ORR in all randomized participants
  • Duration of Response (DOR) [ Time Frame: Up to approximately 3.5 years ]
    DOR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Disease Control Rate [ Time Frame: Up to approximately 3.5 years ]
    Disease Control Rate in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Mean Subjective Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Baseline up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Stomach Cancer Related Symptom Mean Subjective Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) [ Time Frame: Up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Change from Baseline in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) [ Time Frame: Baseline up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Mean Subjective Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) [ Time Frame: Up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Change from Baseline of Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) [ Time Frame: Baseline up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Time to Deterioration in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) [ Time Frame: Up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score [ Time Frame: Up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score [ Time Frame: Up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Time to Deterioration in Physical Function Score as Measured by a Subscale of European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Day 1 up to approximately 3.5 years ]
    Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants
  • Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma [ Time Frame: Day 1 up to approximately 3.5 years ]
  • Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab in Combination with mFOLFOX6 in Plasma [ Time Frame: Day 1 up to approximately 3.5 years ]
  • Number of Participants with an Anti-bemarituzumab Antibody Formation [ Time Frame: Day 1 up to approximately 3.5 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2021)
  • Progression-free Survival (PFS) [ Time Frame: Up to approximately 3.5 years ]
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 3.5 years ]
  • Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to approximately 3.5 years ]
  • Duration of Response (DOR) [ Time Frame: Up to approximately 3.5 years ]
  • Disease Control Rate [ Time Frame: Up to approximately 3.5 years ]
  • Mean Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Up to approximately 3.5 years ]
  • Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Baseline up to approximately 3.5 years ]
  • Stomach Cancer Related Symptom Mean Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) [ Time Frame: Up to approximately 3.5 years ]
  • Change from Baseline in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) [ Time Frame: Baseline up to approximately 3.5 years ]
  • Mean Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) [ Time Frame: Up to approximately 3.5 years ]
  • Change from Baseline Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) [ Time Frame: Baseline up to approximately 3.5 years ]
  • Time to Deterioration in Stomach Cancer Related Symptom Score as Measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Stomach (EORTC-QLQ-STO22) [ Time Frame: Up to approximately 3.5 years ]
  • Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score [ Time Frame: Up to approximately 3.5 years ]
  • Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score [ Time Frame: Up to approximately 3.5 years ]
  • Time to Deterioration in Physical Function Score as Measured by a Subscale of European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) [ Time Frame: Day 1 up to approximately 3.5 years ]
  • Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma [ Time Frame: Day 1 up to approximately 3.5 years ]
  • Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab in Combination with mFOLFOX6 in Plasma [ Time Frame: Day 1 up to approximately 3.5 years ]
  • Number of Participants with an Anti-bemarituzumab Antibody Formation [ Time Frame: Day 1 up to approximately 3.5 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
Official Title  ICMJE A Randomized, Multi-center, Double-blind, Placebo-controlled Phase 3 Study of Bemarituzumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Subjects With Previously Untreated Advanced Gastric or Gastroesophageal Junction Cancer With FGFR2b Overexpression
Brief Summary The main objective of this study is to compare efficacy of bemarituzumab combined with oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (mFOLFOX6) to placebo plus mFOLFOX6 as assessed by overall survival (OS) in participants with FGFR2b ≥10% 2+/3+ tumor cell staining (FGFR2b ≥10% 2+/3+TC)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma
Intervention  ICMJE
  • Drug: Bemarituzumab
    Intravenous (IV) infusion
  • Drug: mFOLFOX6
    mFOLFOX6 administered as a combination of oxaliplatin and leucovorin as IV infusions. 5-FU administered as bolus followed by additional administration as IV infusion.
  • Drug: Placebo
    IV infusion
Study Arms  ICMJE
  • Experimental: Bemarituzumab with mFOLFOX6
    Interventions:
    • Drug: Bemarituzumab
    • Drug: mFOLFOX6
  • Active Comparator: Placebo with mFOLFOX6
    Interventions:
    • Drug: mFOLFOX6
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 13, 2021)
516
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 18, 2025
Estimated Primary Completion Date August 18, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults with histologically documented unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy
  • Fibroblast growth factor receptor 2b (FGFR2b) ≥10% 2+/3+ tumor cell staining as determined by centrally performed immunohistochemistry (IHC) testing, based on tumor sample either archival (obtained within 6 months/180 days prior to signing pre-screening informed consent) or a fresh biopsy
  • Eastern Cooperative Oncology Group (ECOG) less than or equal to 1
  • Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) V 1.1
  • Participant has no contraindications to mFOLFOX6 chemotherapy
  • Adequate organ and bone marrow function:

    • absolute neutrophil count greater than or equal to 1.5 times 10^9/L
    • platelet count greater than or equal to 100 times 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 aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times the upper limit of normal (ULN) (or less than 5 times ULN if liver involvement). Total bilirubin less than 1.5 times ULN (or less than 2 times ULN if liver involvement); with the exception of participants with Gilbert's disease)
    • calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age]) × Mass [kg]/[72 × Creatinine mg/dL]) (x 0.85 if female)
    • international normalized ratio (INR) or prothrombin time (PT) less than 1.5 times ULN except for participants receiving anticoagulation, who must be on a stable dose of anticoagulant therapy for 6 weeks prior to enrollment

Exclusion Criteria:

  • Prior treatment for metastatic or unresectable disease (Note: prior adjuvant, neo-adjuvant, and peri-operative therapy is allowed if completed more than 6 months prior to first dose of study treatment)
  • Prior treatment with any selective inhibitor of fibroblast growth factor - fibroblast growth factor receptor (FGF-FGFR) pathway
  • Known human epidermal growth factor receptor 2 (HER2) positive
  • Untreated or symptomatic central nervous system (CNS) disease or brain metastases
  • Peripheral sensory neuropathy greater than or equal to Grade 2
  • Clinically significant cardiac disease
  • Other malignancy within the last 2 years (exceptions for definitively treated disease)
  • Chronic or systemic ophthalmological disorders
  • Major surgery or other investigational study within 28 days prior to first dose of study treatment
  • Palliative radiotherapy within 14 days prior to the first dose of study treatment
  • Evidence of or recent history (within 6 months) of corneal defects, corneal ulcerations, keratitis, or keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   Colombia,   Czechia,   Denmark,   Estonia,   France,   Greece,   Hungary,   Italy,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Poland,   Portugal,   Romania,   Singapore,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05052801
Other Study ID Numbers  ICMJE 20210096
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: 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: https://www.amgen.com/datasharing
Current Responsible Party Amgen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amgen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date February 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP