Untreated Advanced Gastric or Gastroesophageal Junction Cancer with FGFR2b Overexpression MedDRA version: 23.1 Level: LLT Classification code 10084227 Term: Gastroesophageal junction cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Adults with unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy 2.Confirmed FGFR2b =10% 2+/3+ TC by centrally performed immunohistochemistry (IHC) testing, based on tumor sample either archival (obtained within 6 months/180 days prior to signing prescreening informed consent) or a fresh biopsy. 3.Eastern Cooperative Oncology Group (ECOG) less than or equal to 1 4.Measurable, evaluable, or non-evaluable disease as long as evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 5.Participant has no contraindications to mFOLFOX6 chemotherapy 6.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 greater than or equal to 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 greater than or equal to 30 mL/minute calculated using the formula of Cockcroft and Gault - 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 warfarin for 6 weeks prior to enrollment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 116
Exclusion criteria
Exclusion criteria: 1.Prior treatment for metastatic or unresectable disease (Note: prior adjuvant or neo-adjuvant therapy for local disease is allowed if ended more than 6 months of 1st dose) 2.Prior treatment with any selective inhibitor of fibroblast growth factor - fibroblast growth factor receptor (FGF-FGFR) pathway 3.Known human epidermal growth factor receptor 2 (HER2) positive 4.Untreated or symptomatic central nervous system (CNS) disease or brain metastases 5.Peripheral sensory neuropathy greater than or equal to Grade 2 6.Clinically significant cardiac disease 7.Other malignancy within the last 2 years (exceptions for definitively treated disease) 8.Chronic or systemic ophthalmological disorders 9.Major surgery or other investigational study within 28 days of randomization 10.Palliative radiotherapy within 14 days of randomization 11.Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare efficacy of bemarituzumab plus mFOLFOX6 to placebo plus mFOLFOX6 as assessed by overall survival (OS) in subjects with FGFR2b = 10% 2+/3+ tumor cell staining (FGFR2b = 10% 2+/3+ TC) ;Secondary Objective: • To compare efficacy between the treatment arms as assessed by progression-free survival (PFS) in FGFR2b = 10% 2+/3+ TC subjects • To compare efficacy between the treatment arms as assessed by objective response (OR) in FGFR2b =10% 2+/3+ TC subjects • To evaluate the safety and tolerability of bemarituzumab plus mFOLFOX6 compared to placebo plus mFOLFOX6 • To compare efficacy of bemarituzumab plus mFOLFOX6 to placebo plus mFOLFOX6 in all randomized subjects as assessed by: - OS, - PFS, - OR • To compare efficacy between treatment arms in FGFR2b =10% 2+/3+ TC subjects as assessed by: - duration of response (DOR) - disease control • To assess patient reported outcomes and QoL outcomes in FGFR2b = 10% 2+/3+ TC subjects • To characterize the PK of bemarituzumab in combination with mFOLFOX6 • To characterize the immunogenicity of bemarituzumab ;Primary end point(s): • Overall survival defined as time from randomization until death from any cause. Subjects still alive will be censored at the date last known to be alive. ;Timepoint(s) of evaluation of this end point: After safety follow-up visit every 3 months (± 1 month) until 214 deaths in FGFR2b = 10% 2+/3+ TC subjects have been observed, or 12 months after the last subject is enrolled, whichever occurs later. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS 2. OR 3. Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE) 4. OS in all randomized subjects 5. PFS in all randomized subjects 6. OR in all randomized subjects 7. Duration of Response (DOR) 8. Disease Control Rate 9. Mean Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) 10. Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQC30) 11. 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) 12. 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) 13. Mean Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) 14. Change from Baseline Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) 15. 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) 16. Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score 17. Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score 18. 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) 19. Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma 20. Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab in Combination with mFOLFOX6 in Plasma | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Czechia, Czech Republic, Denmark, Estonia, France, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United States
Contacts
Public ContactMedical Information
Amgen N.V.
Outcome results
None listed