A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer

Phase 2

Completed

Conditions: Gastric Cancer

Interventions: Biological: Bemarituzumab
Drug: Placebo
Drug: Modified FOLFOX6

Registration Number: NCT03694522

Lead Sponsor: Five Prime Therapeutics, Inc.

Brief Summary: The main objective of the Phase 2 part of the study is to evaluate the efficacy of bemarituzumab (FPA144), a targeted antibody, in combination with modified FOLFOX6 compared to placebo in combination with modified FOLFOX6 in participants with advanced gastrointestinal cancer.

Detailed Description: Study FPA144-004 is a phase 1/2, multicenter, global, double-blind, randomized, controlled study designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of bemarituzumab in combination with mFOLFOX6, compared with placebo in combination with mFOLFOX6, in adults with unresectable, locally advanced, or metastatic gastric cancer including cancer of the gastroesophageal junction (GEJ).

This study includes a Phase 1 safety run-in portion and a Phase 2 portion. The Phase 1 safety run-in is an open-label dose-escalation of bemarituzumab + mFOLFOX6 in patients with GI tumors (not FGFR2 selected) that is reported separately (NCT03343301).

The Phase 2 portion of the study (to follow the Phase 1 safety run-in) is described in this record.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 155

Inclusion Criteria

Histologically documented gastric or gastroesophageal junctional adenocarcinoma (not amenable to curative therapy)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Adequate hematological, liver and kidney function. Measurable or non-measurable, but evaluable disease using RECIST v1.1
Fibroblast growth factor receptor 2b (FGFR2b) overexpression as determined by a centrally performed immunohistochemistry tissue test and/or FGFR2 gene amplification as determined by a centrally performed circulating tumor deoxyribonucleic acid (ctDNA) blood based assay
Candidate for mFOLFOX6 chemotherapy

Key

Exclusion Criteria

Untreated or symptomatic central nervous system (CNS) metastases
Clinically significant cardiac disease,
Peripheral sensory neuropathy >/= Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
Active infection requiring systemic treatment
Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection
Prior treatment with any selective inhibitor of the fibroblast growth factor (FGF)-FGFR pathway
Known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer
Known positivity for human epidermal growth factor receptor 2 (HER2)
Women who are pregnant or breastfeeding

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bemarituzumab + mFOLFOX6	Modified FOLFOX6	Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Bemarituzumab + mFOLFOX6	Bemarituzumab	Participants received 15 mg/kg bemarituzumab administered every 2 weeks (Q2W) with a single additional bemarituzumab 7.5 mg/kg dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Placebo + mFOLFOX6	Placebo	Participants received placebo for bemarituzumab administered every 2 weeks with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.
Placebo + mFOLFOX6	Modified FOLFOX6	Participants received placebo for bemarituzumab administered every 2 weeks with a single additional placebo dose on cycle 1 day 8. Participants also received mFOLFOX6 chemotherapy administered Q2W. Treatment continued until unacceptable toxicity, disease progression, or death.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.	PFS was defined as time from randomization until the date of radiographic disease progression based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death from any cause, whichever came first. PFS was analyzed using Kaplan-Meier methods. Participants with no progression or death, or who started new anticancer therapy before documented progression or death without documented progression, or who had ≥ 2 consecutive missing tumor assessments before documented progression or death without documented progression were censored on the date of last adequate tumor assessment. Participants with no baseline tumor assessment, were censored at the date of randomization. The primary efficacy analysis was pre-specified to be conducted after at least 84 PFS events were observed.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization until the primary analysis data cut-off date of 23 September 2020; median time on follow-up was 10.9 months.	OS is defined as time from randomization until death from any cause. Participants who were lost to follow-up or did not have a date of death were censored at the last date that they were known to be alive. Participants with confirmed death or alive status after the data cutoff date were censored at the data cutoff date. Median OS was estimated using a Kaplan-Meier analysis.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From first dose of study drug to 28 days after last dose of study drug. Actual median (min, max) duration of treatment emergent period was 29 (4.1, 157) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 133) weeks in the placebo + mFOLFOX6 group.	TEAEs are defined as adverse events (AEs) that started or worsened from the start of study drug to 28 days after permanent discontinuation of study drug. A serious AE is defined as any untoward medical occurrence that: * Resulted in death; * Was life-threatening; * Required inpatient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability or incapacity; * Was a congenital anomaly or birth defect. The investigator assessed the causality/relationship between study treatment and each AE, and assessed the severity of each AE according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 on a scale from mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), or death due to the AE (Grade 5). Cornea and retina AEs were defined by Standardized Medical Dictionary for Regulatory Activities Queries (SMQs) of corneal disorders and retinal disorders (broad).
Overall Response Rate (ORR)	Tumor assessments were performed every 8 weeks until 12 months and then every 12 weeks thereafter until disease progression or additional anticancer therapy was initiated; the median duration of follow-up time was 10.9 months.	Tumor response assessment was performed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines. ORR is defined as the percentage of participants who achieved a best overall response (BOR) of either complete response (CR) or partial response (PR) based on investigator assessment of tumor lesions per RECIST v1.1. CR was defined as the disappearance of all lesions except lymph node short axis \< 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions.

Trial Locations

Locations (189): University of Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
The Oncology Institute of Tuscon
🇺🇸
Tucson, Arizona, United States
Marin Cancer Care, Inc-California Cancer Care A Medical Group, Inc
🇺🇸
Greenbrae, California, United States
Sutter Medical Group
🇺🇸
Sacramento, California, United States
UCLA Medical Centre - Santa Monica Hematology and Oncology
🇺🇸
Santa Monica, California, United States
Innovative Clinical Research Institute (ICRI)
🇺🇸
Whittier, California, United States
Yale Cancer Center
🇺🇸
New Haven, Connecticut, United States
Hartford Healthcare Cancer Institute at The Hospital of Central Connecticut
🇺🇸
Plainville, Connecticut, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸
Warrenville, Illinois, United States
Scroll for more (179 remaining)
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States