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

FIGHT: A Phase 3 Randomized, Double-Blind, Controlled Study Evaluating FPA144 and Modified FOLFOX6 in Patients With Previously Untreated Advanced Gastric and Gastroesophageal Cancer: Phase 2 Preceded by Dose Finding in Phase 1

The primary objective of the phase 1 portion of this study is to determine the recommended dose of bemarituzumab in combination with 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) to use in the phase 2 portion of the trial.

Phase 1 is an open-label dose-escalation of bemarituzumab in combination with modified FOLFOX6 (mFOLFOX6). Eligible patients will have unresectable locally advanced or metastatic GI cancer of any type and be candidates to receive at least 2 doses of mFOLFOX6 chemotherapy. Phase 1 consists of 2 dosing cohorts of bemarituzumab in combination with mFOLFOX6 to determine the recommended dose of bemarituzumab in combination with mFOLFOX6 for the phase 2 portion of the study (see study record NCT03694522).

Inclusion Criteria:

1. Disease that is unresectable, locally advanced, or metastatic (not amendable to curative therapy)

2. Understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form (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 childbearing potential 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
   • Women of childbearing potential 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

   • Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L
   • Platelets ≥ 100 × 10^9/L
   • Hemoglobin ≥ 9 g/dL

   Hepatic Function

   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × upper limit of normal (ULN); if liver metastases, then < 5 × ULN
   • Bilirubin < 1.5 × ULN except in patients with Gilbert's disease

   Renal Function

   • Calculated creatinine clearance 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. International normalized ratio (INR) or prothrombin time (PT) < 1.5 x 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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

10. Histologically or cytologically confirmed GI malignancy for which mFOLFOX6 is considered an appropriate treatment (e.g., gastric cancer [GC], colorectal carcinoma, pancreatic adenocarcinoma)

11. Patient must be a candidate to receive at least 2 doses of mFOLFOX6 chemotherapy

Exclusion Criteria:

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):

   1. Unstable angina pectoris ≤ 6 months prior to enrollment
   2. Acute myocardial infarction ≤ 6 months prior to enrollment
   3. New York Heart Association Class II-IV congestive heart failure
   4. Uncontrolled hypertension (as defined as ≥ 160/90 despite optimal medical management)
   5. Uncontrolled cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
   6. Active coronary artery disease
   7. Fridericia's corrected QT interval (QTcF) ≥ 480

3. Peripheral sensory neuropathy ≥ Common Terminology Criteria for Adverse Events (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 (e.g., 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 (e.g., AZD4547, BGJ398, JNJ-42756493, BAY1179470) of the fibroblast growth factor (FGF)-FGFR pathway

10. Ongoing adverse effects from prior systemic treatment > 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 human epidermal growth factor receptor 2 (HER2) (as defined by a positive immunohistochemistry [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); women of childbearing potential must not consider getting pregnant during the study

16. Presence of any serious or unstable concomitant systemic disorder incompatible with the clinical study (e.g., 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 including polysorbate or to platinum-containing medications, 5-FU, or leucovorin

19. History of prior malignancy, except (Criteria a through f):

    1. Curatively treated non-melanoma skin malignancy
    2. Cervical cancer in situ
    3. Curatively treated Stage I uterine cancer
    4. Curatively treated ductal or lobular breast carcinoma in situ and not currently receiving any systemic therapy
    5. Localized prostate cancer that has been treated surgically with curative intent and presumed cured
    6. Solid tumor treated curatively more than 5 years previously without evidence of recurrence