Advanced Gastric and Gastroesophageal Cancer MedDRA version: 20.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: bemarituzumab
Product Code: FPA144
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: bemarituzumab
Current S
Sponsors
Five Prime Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase 1 and Phase 3: 1. Disease that is unresectable, locally advanced, or metastatic (not amenable to curative therapy) 2. Understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF prior to any study-specific evaluation 3. Life expectancy of at least 3 months in the opinion of the investigator 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 5. Age = 18 years at the time the ICF is signed 6. In sexually active patients (women of child bearing potential [WOCBP] and males), willingness to use 2 effective methods of contraception, of which 1 must be a physical barrier method (condom, diaphragm, or cervical/vault cap) until 6 months after the last dose of FPA144. Other effective forms of contraception include: • Permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral tubal ligation with surgery, or vasectomy) at least 6 months prior to screening • WOCBP who are on stable oral contraceptive therapy or intrauterine or implant device for at least 90 days prior to the study, or abstain from sexual intercourse as a way of living 7. Adequate hematological and biological function, confirmed by the following laboratory values within 96 hours prior to enrollment: Bone Marrow Function • ANC = 1.5 × 109/L • Platelets = 100 × 109/L • Hemoglobin = 9 g/dL Hepatic Function • AST and ALT < 3 × ULN; if liver metastases, then < 5 × ULN • Bilirubin < 1.5 × ULN except in patients with Gilbert’s disease Renal Function • Calculated CrCl using Cockroft Gault formula = 50 mL/min 8. INR or prothrombin time (PT) < 1.5 × the ULN except for patients receiving anticoagulation, who must be on a stable dose of warfarin for 6 weeks prior to enrollment 9. Measurable or non-measurable, but evaluable disease using RECIST v1.1 Additional Inclusion Criteria for Phase 3 Only: • Histologically documented gastric or gastroesophageal junction (GEJ) adenocarcinoma (not amenable to curative therapy) • Radiographic imaging of the chest, abdomen and pelvis (computed tomography [CT] preferred, magnetic resonance imaging [MRI] acceptable) performed within 28 days (± 3 days) of treatment (C1D1) • FGFR2b overexpression as determined by a centrally performed IHC tissue test and/or FGFR2 gene amplification as determined by a centrally performed ctDNA blood based assay • Patient must be a candidate for mFOLFOX6 chemotherapy • No prior chemotherapy for metastatic or unresectable disease (except a maximum of 1 dose of mFOLFOX6 administered while waiting for results of FGFR2 testing during the Pre-Screening period) • If prior adjuvant or neo-adjuvant therapy (chemotherapy and/or chemoradiation) has been received, more than 6 months must have elapsed between the end of adjuvant therapy and the confirmation of radiographic disease progression Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes
Exclusion criteria
Exclusion criteria: Phase 1 and Phase 3: 1. Untreated or symptomatic central nervous system (CNS) metastases (CNS imaging not required). Patients with asymptomatic CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and do not require intervention such as surgery, radiation, or any corticosteroid therapy for management of symptoms related to CNS disease 2. Impaired cardiac function or clinically significant cardiac disease, including any of the following (Criteria a through g): a) Unstable angina pectoris = 6 months prior to enrollment b) Acute myocardial infarction = 6 months prior to enrollment c) New York Heart Association Class II-IV congestive heart failure d) Uncontrolled hypertension (as defined as = 160/90 despite optimal medical management) e) Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin f) Active coronary artery disease g) Fridericia’s correction formula (QTcF) = 480 3) Peripheral sensory neuropathy = CTCAE Grade 2 4. Active infection requiring systemic treatment or any uncontrolled infection =14 days prior to enrollment 5. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or known active or chronic hepatitis B or C infection 6. History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) 7. Evidence or history of bleeding diathesis or coagulopathy 8. Radiotherapy = 28 days of enrollment. Patients must be recovered from all acute radiotherapy-related toxicities. No radiopharmaceuticals (strontium, samarium) within 8 weeks of enrollment 9. Prior treatment with any selective inhibitor (eg, AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the FGF-FGFR pathway 10. Ongoing adverse effects from prior systemic treatment > NCI CTCAE Grade 1 (with the exception of Grade 2 alopecia) 11. Participation in another therapeutic clinical study or receiving any investigational agent within 28 days of enrollment or during this clinical study 12. Corneal defects, corneal ulcerations, keratitis, keratoconus, history of corneal transplant, or other known abnormalities of the cornea that may pose an increased risk of developing a corneal ulcer 13. Known positivity for HER2 (as defined by a positive IHC test of 3+ or IHC of 2+ with fluorescent in situ hybridization [FISH]) 14. Major surgical procedures not permitted = 28 days prior to enrollment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before enrollment. In all cases, the patient must be sufficiently recovered and stable before treatment administration 15. Women who are pregnant or breastfeeding (unless the patient is willing to interrupt breastfeeding during study treatment administration and then resume 6 months after study discontinuation); WOCBP must not consider getting pregnant during the study 16. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse, psychiatric disturbance, uncontrolled intercurrent illness including arteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare OS in patients with FGFR2-selected GC treated with FPA144 + mFOLFOX6 to those treated with placebo combined with mFOLFOX6 (hereinafter referred to as [placebo +mFOLFOX6]); Secondary Objective: To compare the following in patients with FGFR2-selected GC treated with FPA144 + mFOLFOX6 to those treated with placebo + mFOLFOX6: • Investigator-assessed progression-free survival (PFS) • Investigator-assessed objective response rate (ORR) • Safety and tolerability To characterize the following: • PK profile of FPA144 + mFOLFOX6 in patients with FGFR2-selected GC • Immunogenicity of FPA144 ;Primary end point(s): Overall survival (OS), defined as time from enrollment until death from any cause;Timepoint(s) of evaluation of this end point: Every 3 months ± 28 days after the End of Treatment visit until up to 24 months after the last patient is enrolled in the study, or until death, loss to follow-up, withdrawal of consent or study termination by the Sponsor (whichever occurs first). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression-free survival (PFS), defined as time from enrollment until the date of radiological disease progression based on investigator assessment (using RECIST v1.1) or death from any cause, whichever comes first • Objective response rate (ORR), defined as the proportion of patients with partial or complete response in all enrolled patients based on investigator assessment of tumor lesions per RECIST v1.1 • Incidence of AEs, clinical laboratory abnormalities, corneal and retinal findings, and ECG abnormalities • Pharmacokinetic (PK) parameters, Cmax and Ctrough of FPA144 in combination with mFOLFOX6 • Incidence of treatment-emergent anti-FPA144 antibody response ; Timepoint(s) of evaluation of this end point: •Radiological/Tumor Assessment: Screening, every 8 weeks from C1D1 until 12 months and then every 12 weeks thereafter, EOT, follow-up (if applicable) •AEs: throughout the study •Laboratory Evaluations: screening; C1D1, C1D8, C2D1, C3D1, C4D1, EoT and as clinically indicated •Vital signs: screening; C1D1, C1D8, C2D1, C3D1, C4D1, EoT; follow-up and as clinically indicated •Ophthalmologic Examination: Screening, every 8 weeks from C1D1, EOT •Slit Lamp Examination: Week 16 and then every 8 weeks through EOT, as clinically indicated, including after EOT •ECG: screening, EoT, as clinically indicated •PK & Immunogenicity Blood Sample collection: Day 1 of Cycles 1, 3, 5, 9, 17 and EoT Where: C1, C2 = Cycle 1, Cycle 2 etc D1, D2 = Day 1, Day 2 etc EoT = End of Treatment | — |
Countries
Australia, Belgium, China, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Portugal, Romania, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactMedical Lead
Five Prime Therapeutics, Inc.
Outcome results
None listed