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

• ClinicalTrials.gov Identifier: NCT05111626
• Recruitment Status: Recruiting
• First Posted: November 8, 2021
• Last Update Posted: May 1, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: October 29, 2021
• First Posted Date: November 8, 2021
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: March 14, 2022
• Estimated Primary Completion Date: September 26, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 18, 2023)

• Part 1: Number of Participants Who Experienced DLTs [ Time Frame: 28 days ]
• Part 1: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 4.5 years ]
• Part 1: Number of Participants Who Experienced One or More Related TEAEs [ Time Frame: Up to 4.5 years ]
• Part 1: Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to 4.5 years ]
• Part 1: Number of Participants With Clinically Significant Changes in Visual Acuity [ Time Frame: Up to 4.5 years ]
• Part 1: Number of Participants With Clinically Significant Changes in Physical Examinations [ Time Frame: Up to 4.5 years ]
• Part 1: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: Up to 4.5 years ]
• Part 2: Overall Survival in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]

Original Primary Outcome Measures (submitted: October 29, 2021)

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

Current Secondary Outcome Measures (submitted: January 26, 2023)

• Part 1: Objective Response (OR) [ Time Frame: Up to 4.5 years ]
• Part 1: Duration of Response (DoR) [ Time Frame: Up to 4.5 years ]
• Part 1: Disease Control Rate (DCR) [ Time Frame: Up to 4.5 years ]
• Part 1: Progression Free Survival (PFS) [ Time Frame: Up to 4.5 years ]
• Part 1: Overall Survival [ Time Frame: Up to 4.5 years ]
• Part 1: Maximum Observed Concentration (Cmax) of Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• Part 1: Area Under the Concentration Time Curve (AUC) of Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• Part 1: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• Part 1: Number of Participants With Anti-Bemarituzumab Antibody Formation [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: PFS in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• Part 2: OR in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants Who Experienced One or More TEAEs [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: Up to 4.5 years ]
• Part 2: Overall Survival in All Randomized Participants [ Time Frame: Up to 4.5 years ]
• Part 2: PFS in All Randomized Participants [ Time Frame: Up to 4.5 years ]
• Part 2: Objective Response Rate (ORR) in All Randomized Participants [ Time Frame: Up to 4.5 years ]
• Part 2: DoR in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• Part 2: DCR in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• 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 in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• Part 2: Change From Baseline in EORTC QLQ-C30 Individual Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Baseline to up to 4.5 years ]
• Part 2: Mean Score in Stomach Cancer Related Symptoms Measured by EORTC Quality of Life Questionnaire-Stomach 22 (QLQ-STO22) in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• Part 2: Change From Baseline in Stomach Cancer Related Symptoms Measured by EORTC QLQ-STO22 in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Baseline to up to 4.5 years ]
• Part 2: Mean Score of Visual Analogue Scale (VAS) Scores as Measured by EuroQol 5-dimensional (EQ-5D-5L) in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Up to 4.5 years ]
• Part 2: Change From Baseline of VAS Scores as Measured by EQ-5D-5L in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Baseline to up to 4.5 years ]
• Part 2: Time to Deterioration in Stomach Cancer Related Symptoms Measured by EORTC QLQ-STO22 in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: Time to Deterioration in Health-Related Quality of Life (HRQoL) Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: Time to Deterioration in Physical Function Scores in FGFR2b ≥ 10% 2+/3+ Tumor Cell Staining Participants [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: Cmax of Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: Ctrough of Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: Number of Participants With Anti-Bemarituzumab Antibody Formation [ Time Frame: Day 1 to up to 4.5 years ]

Original Secondary Outcome Measures (submitted: October 29, 2021)

• Part 1 & 2: Objective Response (OR) [ Time Frame: Up to 4.5 years ]
• Part 1 & 2: Duration of Response (DoR) [ Time Frame: Up to 4.5 years ]
• Part 1 & 2: Disease Control Rate (DCR) [ Time Frame: Up to 4.5 years ]
• Part 1 & 2: Progression Free Survival (PFS) [ Time Frame: Up to 4.5 years ]
• Part 1: Overall Survival [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants With Clinically Significant Changes in Vital Signs [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity [ Time Frame: Up to 4.5 years ]
• Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [ Time Frame: Up to 4.5 years ]
• Part 1: Area Under the Concentration Time Curve (AUC) for Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• Part 1 & 2: Maximum Observed Concentration (Cmax) for Bemarituzumab [ Time Frame: Day 1 to up to 4.5 years ]
• 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 ]
• Part 1 & 2: Number of Participants With Anti-Bemarituzumab Antibody Formation [ Time Frame: Day 1 to up to 4.5 years ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• 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 ]
• Part 2: Time to Deterioration in Health-Related Quality of Life (HRQoL) Scores [ Time Frame: Day 1 to up to 4.5 years ]
• Part 2: Time to Deterioration in Physical Function Scores [ Time Frame: Day 1 to up to 4.5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer
• 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

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 chemotherapy (mFOLFOX6 or capecitabine combined with oxaliplatin (CAPOX)) and nivolumab to placebo plus chemotherapy (mFOLFOX6 or CAPOX) and nivolumab as assessed by overall survival.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Sequential 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 508 participants

Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition

• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma

Intervention

• Drug: Bemarituzumab
  Bemarituzumab will be administered as intravenous (IV) infusion.
  Other Name: AMG 552
• Drug: Nivolumab
  Nivolumab will be administered as IV infusion.
• Drug: Chemotherapy

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

  OR CAPOX: oxaliplatin will be administered as IV infusion and capecitabine will be administered orally.

• Other: Placebo
  Placebo will be administered as IV infusion.

Study Arms

• 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 occurrence of dose-limiting toxicities (DLTs), and on an evaluation of the overall safety, tolerability, and pharmacokinetics (PK).
  Interventions:

  • Drug: Bemarituzumab
  • Drug: Nivolumab
  • Drug: Chemotherapy
• Experimental: Part 2: Bemarituzumab with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab

  Participants will be administered bemarituzumab at the RP3D determined from Part 1 in combination with mFOLFOX6 and nivolumab on a 14-day cycle.

  Or participants will be administered bemarituzumab in combination with CAPOX and nivolumab on a 21-day cycle.

  Interventions:

  • Drug: Bemarituzumab
  • Drug: Nivolumab
  • Drug: Chemotherapy
• Placebo Comparator: Part 2: Placebo with chemotherapy (mFOLFOX6 or CAPOX) and Nivolumab

  Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab on a 14-day cycle.

  Or participants will be administered placebo comparator in combination with CAPOX and nivolumab on a 21-day cycle.

  Interventions:

  • Drug: Nivolumab
  • Drug: Chemotherapy
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 26, 2023): 528
• Original Estimated Enrollment (submitted: October 29, 2021): 702
• Estimated Study Completion Date: September 26, 2026
• Estimated Primary Completion Date: September 26, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria Part 1 and Part 2:

• 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 nivolumab and either mFOLFOX6 or CAPOX chemotherapy as per local prescribing information. Participants in Part 1 must have no contraindications to mFOLFOX6. Participants in Part 2 with contraindications to mFOLFOX6 are permitted and may be administered the CAPOX regimen, if no contraindications for this regimen exist. Participants in Part 2 with contraindications to CAPOX are permitted and may be administered the mFOLFOX6 regimen, if no contraindications for this regimen exist

• 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)
  • Part 1 only: Calculated or measured creatinine clearance (CrCl) of ≥ 50 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age] × Mass [kg]/[72 × Creatinine mg/dL]) (x 0.85 if female).
• Part 2 only: 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).
• 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 chemotherapy 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) ≥ 10% 2+/3+ tumor cells (TC) 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.

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

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, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Portugal, Romania, Singapore, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States

Administrative Information

• NCT Number: NCT05111626
• Other Study ID Numbers: 20210098; 2023-505458-16 ( 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: http://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: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: April 2024