A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 in Gastric/Gastroesophageal Cancer
Condition: Gastrointestinal Cancer; Gastrointestinal Cancer Metastatic; Gastric Cancer
MeSH terms: Gastrointestinal Neoplasms
Intervention: Bemarituzumab; Modified FOLFOX6
Intervention description: Administered by intravenous infusion over approximately 30 minutes; Modified FOLFOX6 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.
Intervention MeSH terms: Bemarituzumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: gastrointestinal cancer

Summary:

      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.
    

Eligibility criteria:

        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