A Phase 2 Study Evaluating FPA144 and Modified FOLFOX6 in Patients with Previously Untreated Advanced Gastric and Gastroesophageal Cancer: Phase I to be conducted prior to Phase 2

Phase 1

• Conditions: Advanced Gastric and Gastroesophageal Cancer; MedDRA version: 21.1Level: PTClassification code 10017758Term: Gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-003507-22-GB
• Lead Sponsor: Five Prime Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-16
• Last Update Posted: 25 August 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 167

Inclusion Criteria

Phase 1 and Phase 2:

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 Cockcroft Gault formula = 50 mL/min or estimated glomerular filtrate rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 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 2 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
F.1.2.1 Number of subjects for this age range 117
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

Phase 1 and Phase 2:

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 and anemia)
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 arterial thrombosis, or symptomatic pulmonary embolism)
17. Presence of any other condition that may increase the risk associated with study participation, or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry in the study
18. Known allergy, hypersensitivity or contraindication to components of the FPA144 formulation includi

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare Investigator-assessed progression-free survival (PFS) 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:<br>• Overall Survival (OS)<br>• Investigator-assessed objective response rate (ORR)<br>• Safety and tolerability<br>;Primary end point(s): Investigator-assessed progression-free survival (PFS) defined as time from randomization until the date of disease progression based on investigator assessment (using RECIST v1.1) or death from any cause, whichever comes first.<br>;Timepoint(s) of evaluation of this end point: Radiological/ Tumour Assessment: Screening, every 8 weeks from C1D1 until 12 months and then every 12 weeks thereafter, EOT, follow-up (if applicable).