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

Phase 1 is an open-label dose-escalation of FPA144 in combination with 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. FGFR2 status is not a
requirement for enrollment. FGFR2 status will be tested retrospectively by
immunohistochemistry (IHC) if tissue is available and a sample will be obtained for
circulating tumor deoxynucleic acid (ctDNA) blood assay. Phase 1 consists of at least 2
dosing cohorts of FPA144 in combination with mFOLFOX6 to determine the recommended dose of
FPA144 in combination with mFOLFOX6 in the phase 3.

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 × 109/L

- Platelets >/= 100 × 109/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 cockroft Gault formula >/= 50 mL/min (see
Appendix 1)

8. 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 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
2. Acute myocardial infarction
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. Fridericiaís 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 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 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 > 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 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