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

• ClinicalTrials.gov Identifier: NCT03694522
• Recruitment Status: Completed
• First Posted: October 3, 2018
• Results First Posted: May 24, 2022
• Last Update Posted: February 28, 2024
• Sponsor: Five Prime Therapeutics, Inc.
• Collaborator: Zai Lab (Shanghai) Co., Ltd.
• Information provided by (Responsible Party): Five Prime Therapeutics, Inc.

Tracking Information

• First Submitted Date: September 14, 2018
• First Posted Date: October 3, 2018
• Results First Submitted Date: April 28, 2022
• Results First Posted Date: May 24, 2022
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: September 14, 2018
• Actual Primary Completion Date: September 23, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 28, 2022)

Progression-Free Survival (PFS) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: October 1, 2018)

Overall Survival (OS) [ Time Frame: up to approximately 46 months ]

Time from enrollment until death from any cause

Current Secondary Outcome Measures (submitted: December 15, 2022)

• Overall Survival (OS) [ Time Frame: 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.
• Overall Response Rate (ORR) [ Time Frame: 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.
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: October 1, 2018)

• Progression-free survival (PFS) [ Time Frame: Up to approximately 46 months ]
  time from enrollment until the EARLIER OF a. progression or b. death from any cause.
• Overall response rate (ORR) [ Time Frame: Up to approximately 46 months ]
  Proportion of patients with partial or complete response based on assessment of tumor lesions per RECIST v1.1
• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 [ Time Frame: Through completion of study treatment, an average of 1 year ]
  Treatment-Emergent Adverse Events (TEAEs) classified by MedDRA preferred term and assessed by CTCAE.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer
• Official Title: FIGHT: A Phase 2 Randomized, Double-Blind, Controlled Study Evaluating Bemarituzumab (FPA144) and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Preceded by Dose-Finding in Phase 1
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Double blinded (participant, treating physician)

Primary Purpose: Treatment

• Condition: Gastric Cancer

Intervention

• Biological: Bemarituzumab
  Administered by intravenous infusion over approximately 30 minutes
  Other Names:

  • FPA144
  • AMG 552
• Drug: Placebo
  Administered by intravenous infusion over approximately 30 minutes
• Drug: Modified FOLFOX6

  mFOLFOX6 regimen consists of the following:

  • Oxaliplatin 85 mg/m² IV infusion over 120 minutes
  • Leucovorin 400 mg/m² IV infusion over 120 minutes, or 200 mg/m² levo-leucovorin if leucovorin is unavailable
  • 5-fluorouracil (5-FU) 400 mg/m² bolus over approximately 5 minutes then 5-FU 2400 mg/m² as a continuous IV infusion over approximately 48 hours
  Other Name: mFOLFOX6

Study Arms

• Experimental: Bemarituzumab + mFOLFOX6
  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.
  Interventions:

  • Biological: Bemarituzumab
  • Drug: Modified FOLFOX6
• Placebo Comparator: Placebo + mFOLFOX6
  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.
  Interventions:

  • Drug: Placebo
  • Drug: Modified FOLFOX6

Publications *

• Wainberg ZA, Enzinger PC, Kang YK, Qin S, Yamaguchi K, Kim IH, Saeed A, Oh SC, Li J, Turk HM, Teixeira A, Borg C, Hitre E, Udrea AA, Cardellino GG, Sanchez RG, Collins H, Mitra S, Yang Y, Catenacci DVT, Lee KW. Bemarituzumab in patients with FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma (FIGHT): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet Oncol. 2022 Nov;23(11):1430-1440. doi: 10.1016/S1470-2045(22)00603-9. Epub 2022 Oct 14.
• Xiang H, Liu L, Gao Y, Ahene A, Macal M, Hsu AW, Dreiling L, Collins H. Population pharmacokinetic analysis of phase 1 bemarituzumab data to support phase 2 gastroesophageal adenocarcinoma FIGHT trial. Cancer Chemother Pharmacol. 2020 Nov;86(5):595-606. doi: 10.1007/s00280-020-04139-4. Epub 2020 Sep 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 4, 2020): 155
• Original Estimated Enrollment (submitted: October 1, 2018): 548
• Actual Study Completion Date: May 13, 2022
• Actual Primary Completion Date: September 23, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, China, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Portugal, Romania, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03694522
• Other Study ID Numbers: FPA144-004 Phase 2; 2017-003507-22 ( EudraCT Number ); 20210113 ( Other Identifier: Amgen )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Five Prime Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Five Prime Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Zai Lab (Shanghai) Co., Ltd.

Investigators

• Study Director: MD; Amgen

• PRS Account: Five Prime Therapeutics, Inc.
• Verification Date: February 2024