A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer (FIGHT)
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| ClinicalTrials.gov Identifier: NCT03694522 |
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Recruitment Status :
Completed
First Posted : October 3, 2018
Results First Posted : May 24, 2022
Last Update Posted : July 6, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Gastric Cancer | Biological: Bemarituzumab Drug: Placebo Drug: Modified FOLFOX6 | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 155 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Masking Description: | Double blinded (participant, treating physician) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | September 14, 2018 |
| Actual Primary Completion Date : | September 23, 2020 |
| Actual Study Completion Date : | May 13, 2022 |
| Arm | Intervention/treatment |
|---|---|
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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.
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Biological: Bemarituzumab
Administered by intravenous infusion over approximately 30 minutes
Other Name: FPA144 Drug: Modified FOLFOX6 mFOLFOX6 regimen consists of the following:
Other Name: mFOLFOX6 |
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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.
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Drug: Placebo
Administered by intravenous infusion over approximately 30 minutes Drug: Modified FOLFOX6 mFOLFOX6 regimen consists of the following:
Other Name: mFOLFOX6 |
- 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.
- 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.
- 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 [ 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, 75.0) weeks in the bemarituzumab + mFOLFOX6 group and 28 (4.3, 75.6) weeks in the placebo + mFOLFOX6 group. ]
Treatment emergent adverse events are defined as adverse events (AEs) that started or worsened between the start of study drug and 28 days after permanent discontinuation of study drug.
A serious AE is defined as any untoward medical occurrence that at any dose:
- 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 the study treatment and each AE, and assessed the severity of each AE according to the guidelines provided in 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).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03694522
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Documents provided by Five Prime Therapeutics, Inc.:
| Responsible Party: | Five Prime Therapeutics, Inc. |
| ClinicalTrials.gov Identifier: | NCT03694522 |
| Other Study ID Numbers: |
FPA144-004 Phase 2 |
| First Posted: | October 3, 2018 Key Record Dates |
| Results First Posted: | May 24, 2022 |
| Last Update Posted: | July 6, 2022 |
| Last Verified: | March 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Stomach Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases |
Gastrointestinal Diseases Stomach Diseases Bemarituzumab Antineoplastic Agents, Immunological Antineoplastic Agents |