臨床研究等提出・公開システム

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

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

Kaneda Hirokazu

Amgen K.K.

Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo

clinicaltrials_japan@amgen.com

Local Contact

Amgen K.K.

Midtown Tower 9-7-1 Akasaka, Minato-ku, Tokyo

+81-80-7217-8592

clinicaltrials_japan@amgen.com

Not Recruiting

Mar. 07, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Adults with histologically documented unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy
2. 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
3. Eastern Cooperative Oncology Group (ECOG) less than or equal to 1
4. Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) V 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 >= 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]) x Mass [kg]/[72 x 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

1. 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)
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 prior to first dose of study treatment
10. Palliative radiotherapy within 14 days prior to the first dose of study treatment
11. 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.

Both

Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

-Experimental: Bemarituzumab with mFOLFOX6
Interventions:
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.

-Active Comparator: Placebo with mFOLFOX6
Interventions:
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

1. Overall Survival [ Time Frame: Up to approximately 3.5 years ]
Overall survival in FGFR2b >= 10% 2+/3+ tumor cell staining participants

1. Progression-free Survival (PFS) [ Time Frame: Up to approximately 3.5 years ]
PFS in FGFR2b >= 10% 2+/3+ tumor cell staining participants
2. Objective Response Rate (ORR) [ Time Frame: Up to approximately 3.5 years ]
ORR in FGFR2b >= 10% 2+/3+ tumor cell staining participants
3. 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.
4. Overall Survival [ Time Frame: Up to approximately 3.5 years ]
Overall survival in all randomized participants
5. Progression-free Survival (PFS) [ Time Frame: Up to approximately 3.5 years ]
PFS in all randomized participants
6. Objective Response Rate (ORR) [ Time Frame: Up to approximately 3.5 years ]
ORR in all randomized participants
7. Duration of Response (DOR) [ Time Frame: Up to approximately 3.5 years ]
DOR in FGFR2b >= 10% 2+/3+ tumor cell staining participants
8. Disease Control Rate [ Time Frame: Up to approximately 3.5 years ]
Disease Control Rate in FGFR2b >= 10% 2+/3+ tumor cell staining participants
9. 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
10. 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
11. 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
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) [ Time Frame: Baseline up to approximately 3.5 years ]
Measured in FGFR2b >= 10% 2+/3+ tumor cell staining participants
13. 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
14. 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
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) [ Time Frame: Up to approximately 3.5 years ]
Measured in FGFR2b >= 10% 2+/3+ tumor cell staining participants
16. Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQC30) Score [ Time Frame: Up to approximately 3.5 years ]
Measured in FGFR2b >= 10% 2+/3+ tumor cell staining participants
17. 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
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) [ Time Frame: Day 1 up to approximately 3.5 years ]
Measured in FGFR2b >= 10% 2+/3+ tumor cell staining participants
19. Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma [ Time Frame: Day 1 up to approximately 3.5 years ]
20. 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 ]
21. Number of Participants with an Anti-bemarituzumab Antibody Formation [ Time Frame: Day 1 up to approximately 3.5 years ]

Jan. 21, 2022

Yes

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

United States/Australia/Belgium/Korea/Latvia/Lithuania/Turkey/Argentina/Brazil/Bulgaria/Canada/Chile/China/Colombia/Czechia/Denmark/Estonia/France/Greece/Hungary/Israel/Italy/Malaysia/Mexico/Poland/Portugal/Romania/Singapore/South Africa/Spain/Sweden/Taiwan/Thailand/Ireland/Norway/Peru