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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

Bemarituzumab Plus Chemotherapy and Nivolumab Versus Chemotherapy and Nivolumab for FGFR2b Overexpressed Untreated Advanced Gastric and Gastroesophageal Junction Cancer

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

Complete

Mar. 31, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

Inclusion Criteria Part 1 and Part 2:
1. Adult with unresectable, locally advanced or metastatic (not amenable to curative therapy) histologically documented gastric or gastroesophageal junction adenocarcinoma
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
3. Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1)
4. 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
5. 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] x Mass [kg]/[72 x 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] x Mass [kg]/[72 x Creatinine mg/dL]) (x 0.85 if female).
- INR or prothrombin time (PT) < 1.5 x 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:
6. 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.
7. 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.

1. Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
2. Known positive human epidermal growth factor receptor 2 (HER2) status
3. Untreated or symptomatic central nervous system disease metastases and leptomeningeal disease
4. Peripheral sensory neuropathy grade 2 or higher
5. Clinically significant cardiac disease
6.Other malignancy within the last 2 years (exceptions for definitively treated disease)
7. Chronic or systemic ophthalmologic disorders
8. Major surgery or other investigational study within 28 days prior to randomization
9. Palliative radiotherapy within 14 days prior to randomization
10. Abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
11. 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

Both

Gastric Cancer, Gastroesophageal Junction Adenocarcinoma

Experimental: Part 1 Safety Lead-in: Bemarituzumab with mFOLFOX6 and Nivolumab
Participants will be administered bemarituzumab at different doses with mFOLFOX6and 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 1in 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

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

1. Part 1: Objective Response (OR) [Time Frame: Up to 4.5 years]
2. Part 1: Duration of Response (DoR) [Time Frame: Up to 4.5 years]
3. Part 1: Disease Control Rate (DCR) [Time Frame: Up to 4.5 years]
4. Part 1: Progression Free Survival (PFS) [Time Frame: Up to 4.5 years]
5. Part 1: Overall Survival [Time Frame: Up to 4.5 years]
6. Part 1: Maximum Observed Concentration (Cmax) of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years]
7. Part 1: Area Under the Concentration Time Curve (AUC) of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years]
8. Part 1: Observed Concentration at the End of a Dose Interval (Ctrough) of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years]
9. Part 1: Number of Participants With Anti-Bemarituzumab Antibody Formation [Time Frame: Day 1 to up to 4.5 years]
10. Part 2: PFS in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Up to 4.5 years]
11. Part 2: Overall Survival in All Randomized Participants [Time Frame: Up to 4.5 years]
12. Part 2: PFS in All Randomized Participants [Time Frame: Up to 4.5 years]
13. Part 2: Number of Participants Who Experienced One or More TEAEs [Time Frame: Up to 4.5 years]
14. Part 2: Number of Participants With Clinically Significant Changes in Vital Signs [Time Frame: Up to 4.5 years]
15. Part 2: Number of Participants With Clinically Significant Changes in Visual Acuity [Time Frame: Up to 4.5 years]
16. Part 2: Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests [Time Frame: Up to 4.5 years]
17. Part 2: OR [Time Frame: Up to 4.5 years]
18. Part 2: DoR [Time Frame: Up to 4.5 years]
19. Part 2: DCR [Time Frame: Up to 4.5 years]
20. 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]
21. 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]
22. 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]
23. 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]
24. 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]
25. 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]
26. Part 2: Time to Deterioration in Stomach Cancer Related Symptoms Measured by EORTC QLQSTO22 in FGFR2b >= 10% 2+/3+ Tumor Cell Staining Participants [Time Frame: Day 1 to up to 4.5 years]
27. 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]
28. 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]
29. Part 2: AUC of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years]
30. Part 2: Cmax of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years]
31. Part 2: Ctrough of Bemarituzumab [Time Frame: Day 1 to up to 4.5 years]
32. Part 2: Number of Participants With Anti-Bemarituzumab Antibody Formation [Time Frame: Day 1 to up to 4.5 years]

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Feb. 02, 2022

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