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

Phase 3Active Not RecruitingNCT05052801

Amgen547 enrolled

Overview

The main objective of this study is to compare efficacy of bemarituzumab combined with oxaliplatin, leucovorin, and 5-fluorouracil (5-FU) (mFOLFOX6) to placebo plus mFOLFOX6 as assessed by overall survival (OS) in participants with FGFR2b ≥10% 2+/3+ tumor cell staining (FGFR2b ≥10% 2+/3+TC)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

547

Conditions

Gastric Cancer Gastroesophageal Junction Adenocarcinoma

Interventions

BemarituzumabDRUG

Intravenous (IV) infusion

mFOLFOX6DRUG

mFOLFOX6 administered as a combination of oxaliplatin and leucovorin as IV infusions. 5-FU administered as bolus followed by additional administration as IV infusion.

PlaceboDRUG

IV infusion

Eligibility

Sex: ALLMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults with histologically documented unresectable, locally advanced or metastatic gastric or gastroesophageal junction cancer not amenable to curative therapy * 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 * Eastern Cooperative Oncology Group (ECOG) less than or equal to 1 * Measurable disease or non-measurable, but evaluable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) V 1.1 * Participant has no contraindications to mFOLFOX6 chemotherapy * 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 (\[140 - Age\]) × Mass \[kg\]/\[72 × Creatinine mg/dL\]) (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 Exclusion Criteria: * 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) * Prior treatment with any selective inhibitor of fibroblast growth factor - fibroblast growth factor receptor (FGF-FGFR) pathway * Known human epidermal growth factor receptor 2 (HER2) positive * Untreated or symptomatic central nervous system (CNS) disease or brain metastases * Peripheral sensory neuropathy greater than or equal to Grade 2 * Clinically significant cardiac disease * Other malignancy within the last 2 years (exceptions for definitively treated disease) * Chronic or systemic ophthalmological disorders * Major surgery or other investigational study within 28 days prior to first dose of study treatment * Palliative radiotherapy within 14 days prior to the first dose of study treatment * 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.

Locations (300)

Outcomes

Primary Outcomes

Overall Survival

Overall survival in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Secondary Outcomes

Progression-free Survival (PFS)

PFS in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Objective Response Rate (ORR)

ORR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Number of Participants who Experience a Treatment-emergent Adverse Event (TEAE)

Any clinically significant changes in vital signs, visual acuity, and clinical laboratory tests after first dose will be recorded as TEAEs.

Time frame: Up to approximately 3.5 years

Overall Survival

Overall survival in all randomized participants

Time frame: Up to approximately 3.5 years

Progression-free Survival (PFS)

PFS in all randomized participants

Time frame: Up to approximately 3.5 years

Objective Response Rate (ORR)

ORR in all randomized participants

Time frame: Up to approximately 3.5 years

Duration of Response (DOR)

DOR in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Data from ClinicalTrials.gov

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Disease Control Rate

Disease Control Rate in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Mean Subjective Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Change from Baseline Score in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Baseline up to approximately 3.5 years

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)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

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)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Baseline up to approximately 3.5 years

Mean Subjective Score in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Change from Baseline of Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Baseline up to approximately 3.5 years

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)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) Score

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

Time to Deterioration in Visual Analogue Scale (VAS) as Measured by the EuroQol 5-dimensional 5-levels (EQ-5D-5L) Score

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Up to approximately 3.5 years

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)

Measured in FGFR2b ≥ 10% 2+/3+ tumor cell staining participants

Time frame: Day 1 up to approximately 3.5 years

Maximum Observed Concentration (Cmax) of Bemarituzumab in Combination with mFOLFOX6 in Plasma

Time frame: Day 1 up to approximately 3.5 years

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

Number of Participants with an Anti-bemarituzumab Antibody Formation

Time frame: Day 1 up to approximately 3.5 years