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

• ClinicalTrials.gov Identifier: NCT05052801
• Recruitment Status: Recruiting
• First Posted: September 22, 2021
• Last Update Posted: May 16, 2024
• Sponsor: Amgen
• Collaborator: Zai Lab (China only)
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: September 13, 2021
• First Posted Date: September 22, 2021
• Last Update Posted Date: May 16, 2024
• Actual Study Start Date: March 7, 2022
• Estimated Primary Completion Date: August 18, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: September 13, 2021): Overall Survival (OS) [ Time Frame: Up to approximately 3.5 years ]

Current Secondary Outcome Measures (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 (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: Bemarituzumab or Placebo Plus Chemotherapy in Gastric Cancers With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma

Intervention

• 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

• Experimental: Bemarituzumab with mFOLFOX6
  Interventions:

  • Drug: Bemarituzumab
  • Drug: mFOLFOX6
• Active Comparator: Placebo with mFOLFOX6
  Interventions:

  • Drug: mFOLFOX6
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 13, 2021): 516
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 18, 2025
• Estimated Primary Completion Date: August 18, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, Denmark, Estonia, France, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Norway, Peru, Poland, Portugal, Romania, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United States

Administrative Information

• NCT Number: NCT05052801
• Other Study ID Numbers: 20210096; 2023-505457-40 ( Registry Identifier: CTIS (EU) )
• 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

• 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: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Zai Lab (China only)

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: May 2024