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 |
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Recruitment Status :
Recruiting
First Posted : November 8, 2021
Last Update Posted : June 1, 2023
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Sponsor:
Amgen
Information provided by (Responsible Party):
Amgen
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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 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 528 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This is a Phase 1b/3 study:
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| 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 : | January 26, 2027 |
| Estimated Study Completion Date : | January 26, 2027 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Nivolumab
| Arm | Intervention/treatment |
|---|---|
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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).
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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. |
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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.
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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. |
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Placebo Comparator: Part 2: Placebo with mFOLFOX6 and Nivolumab
Participants will be administered placebo comparator in combination with mFOLFOX6 and nivolumab.
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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 :
- 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 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 ]
Secondary Outcome Measures :
- 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 ]
Information from the National Library of Medicine
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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 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 mFOLFOX6 chemotherapy or nivolumab
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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) ≥ 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
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
| Contact: Amgen Call Center | 866-572-6436 | medinfo@amgen.com |
Locations
Show 163 study locations
Sponsors and Collaborators
Amgen
Investigators
| Study Director: | MD | Amgen |
Additional Information:
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT05111626 |
| Other Study ID Numbers: |
20210098 |
| First Posted: | November 8, 2021 Key Record Dates |
| Last Update Posted: | June 1, 2023 |
| Last Verified: | May 2023 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Amgen:
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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 |