FORTITUDE-102: Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer
Study Details
Study Description
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 |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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 Names:
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 Names:
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.
|
Outcome Measures
Primary Outcome Measures
- Part 1: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [28 days]
- Part 1: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [Up to 4.5 years]
- Part 1: Number of Participants Who Experienced One or More Related TEAEs [Up to 4.5 years]
- Part 1: Number of Participants With Clinically Significant Changes in Vital Signs [Up to 4.5 years]
- Part 1: Number of Participants With Clinically Significant Changes in Visual Acuity [Up to 4.5 years]
- Part 1: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) [Up to 4.5 years]
- Part 1: Number of Participants With Clinically Significant Changes in Physical Examinations [Up to 4.5 years]
- Part 1: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [Up to 4.5 years]
- Part 2: Overall Survival [Up to 4.5 years]
Secondary Outcome Measures
- Part 1 & 2: Objective Response (OR) [Up to 4.5 years]
- Part 1 & 2: Duration of Response (DoR) [Up to 4.5 years]
- Part 1 & 2: Disease Control Rate (DCR) [Up to 4.5 years]
- Part 1 & 2: Progression Free Survival (PFS) [Up to 4.5 years]
- Part 1: Overall Survival [Up to 4.5 years]
- Part 2: Number of Participants Who Experienced One or More Treatment-Emergent Adverse Events (TEAEs) [Up to 4.5 years]
- Part 2: Number of Participants With Clinically Significant Changes in Vital Signs [Up to 4.5 years]
- Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity [Up to 4.5 years]
- Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [Up to 4.5 years]
- Part 1: Area Under the Concentration Time Curve (AUC) for Bemarituzumab [Day 1 to up to 4.5 years]
- Part 1 & 2: Maximum Observed Concentration (Cmax) for Bemarituzumab [Day 1 to up to 4.5 years]
- Part 1 & 2: Observed Concentration at the End of a Dose Interval (Ctrough) for Bemarituzumab [Day 1 to up to 4.5 years]
- Part 1 & 2: Number of Participants With Anti-Bemarituzumab Antibody Formation [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 [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 [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) [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) [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) [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) [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) [Day 1 to up to 4.5 years]
- Part 2: Time to Deterioration in Health-Related Quality of Life (HRQoL) Scores [Day 1 to up to 4.5 years]
- Part 2: Time to Deterioration in Physical Function Scores [Day 1 to up to 4.5 years]
Eligibility Criteria
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
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Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
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Participant has no contraindications to mFOLFOX6 chemotherapy or nivolumab
-
Adequate organ function as follows:
-
Absolute neutrophil count ≥ 1.5 x 10^9/L
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Platelet count ≥ 100 x 10^9/L
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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)
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Total bilirubin <1.5 x ULN (or < 2 x ULN if liver involvement or Gilbert's disease)
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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
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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
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Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease
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Peripheral sensory neuropathy grade 2 or higher
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Clinically significant cardiac disease
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Other malignancy within the last 2 years (exceptions for definitively treated disease)
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Chronic or systemic ophthalmologic disorders
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Major surgery or other investigational study within 28 days prior to randomization
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Palliative radiotherapy within 14 days prior to randomization
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic - Arizona | Phoenix | Arizona | United States | 85054 |
| 2 | City of Hope National Medical Center | Duarte | California | United States | 91010 |
| 3 | University of California Los Angeles Bowyer Hematology-Oncology Clinic | Los Angeles | California | United States | 90095 |
| 4 | University of California at Irvine Medical Center | Orange | California | United States | 92868 |
| 5 | Innovative Clinical Research Institute | Whittier | California | United States | 90603 |
| 6 | Mayo Clinic Florida | Jacksonville | Florida | United States | 32224 |
| 7 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
| 8 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10022 |
| 9 | The West Clinic, PLLC | Germantown | Tennessee | United States | 38138 |
| 10 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 11 | Texas Oncology - Austin Midtown | Austin | Texas | United States | 78705 |
| 12 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 13 | Virginia Oncology Associates | Norfolk | Virginia | United States | 23502 |
| 14 | Northwest Cancer Specialists - Vancouver | Vancouver | Washington | United States | 98684 |
| 15 | The Queen Elizabeth Hospital | Woodville South | South Australia | Australia | 5011 |
| 16 | National Cancer Center Hospital East | Kashiwa-shi | Chiba | Japan | 277-8577 |
| 17 | The Cancer Institute Hospital of Japanese Foundation for Cancer Research | Koto-ku | Tokyo | Japan | 135-8550 |
| 18 | Ninewells Hospital and Medical School | Dundee | United Kingdom | DD1 9SY |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 20210098