Lucitanib (E3810) in Patients With Advanced Cancer and FGFR, VEGFR, or PDGFR Pathway Aberrations

Lucitanib is an oral multi kinase inhibitor designed to block the action of certain molecules
called "angiogenic factors" that may cause tumors to grow. These factors are called vascular
endothelial growth factor (called VEGF), platelet derived growth factor receptor (PDGFR) and
fibroblast growth factor (called FGF). Lucitanib is experimental and not approved by the FDA
for the treatment of cancer.

The purpose of this clinical trial is to study the following in cancer patients whose cancers
harbor aberrations in FGFR, VEGFR, PDGFR, or other biomarkers predicted to be sensitive to
lucitanib:

- To look at the effects of lucitanib on their disease at 10 mg once daily.

- To look for biomarkers in samples of blood and tumor tissue to identify patients most
likely to respond to lucitanib.

- To look at the safety of lucitanib in these patients

This is a two-center, open-label, non-randomized Phase II study of lucitanib in adult
subjects with advanced cancers. Treatment will consist of daily oral administration of 10mg
of lucitanib in 28-day cycles.

All patients providing informed consent will be screened for eligibility. Baseline
assessments will include vital signs, physical exam, blood hematology and chemistries, ECG,
and ECHO. If not done within the prior 4 weeks, a PET/CT scan, MRI, and/or CT scan will be
performed for radiological evaluation of disease.

Clinical evaluations include physical exam, vitals, ECG (obtained once every month throughout
treatment); blood hematology and chemistries (obtained every two weeks for the first three
months and then once every month throughout treatment); radiologic evaluations (PET/CT, CT
and/or MRI, +/- bone imaging as clinically appropriate) will be performed every 8 weeks.

This study may last up to approximately 4 years or longer, depending on whether or not the
study doctor feels that continuing lucitanib dosing is in the patient's best interest. Once a
patient finishes study treatment with lucitanib, patients will need to complete an End of
Study visit. Each of the study visits can last from approximately 2 to 8 hours.

Inclusion Criteria:

- Pathologically confirmed advanced or metastatic malignancy characterized by one or
more of the following:

- Subject is intolerant of standard therapy

- Malignancy is refractory to standard therapy

- Malignancy relapsed after standard therapy

- Malignancy for which there is no standard therapy that improves survival by at
least 3 months.

- Subjects must have evaluable tumor(s) with documented alteration(s) in potential
lucitanib related biomarker(s) VEGFR, FGFR, PDGFR.

- Laboratory function within specified parameters:

- Adequate bone marrow function: absolute neutrophil count ≥ 1,500/mL; hemoglobin ≥
8.5 g/dL, platelets ≥ 75,000/mL.

- Adequate liver function: transaminases (AST/ALT) and alkaline phosphatase ≤ 3 (≤
5 X ULN in the setting of liver metastasis) x ULN; bilirubin ≤ 1.5 x ULN.

- Adequate renal function: creatinine clearance ≥ 40 mL/min (Cockcroft Gault).

- Adequate blood coagulation: international normalized ratio (INR) ≤ 2.3.

- Serum amylase and lipase ≤ 1.5 x ULN.

- Adequately controlled blood pressure (BP): BP ≤ 150/90 mm Hg. Use of > 2
antihypertensive agents at enrollment is not allowed.

- Adequate performance status: Eastern Cooperative Oncology Group (ECOG) 0-2

- Subjects must be off other anti-tumor agents for at least 5 half lives of the agent or
4 weeks from the last day of treatment, whichever is shorter. Endocrine therapies
(e.g., for breast or prostate cancer) and anti-Her2 therapies (for example,
trastuzumab, pertuzumab, or lapatinib) are allowed to continue while on this study.
Bisphosphonates or denosumab are allowed for subjects with bone metastasis.

- Subjects may not be receiving any other experimental agents or agents that are not FDA
approved.

Exclusion Criteria:

- Pregnant or lactating women.

- Uncontrolled hypertension (defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg with
optimized antihypertensive therapy)

- Subjects who have not recovered from toxicities as a result of prior anticancer
therapy, except alopecia and infertility. Recovery is defined as < Grade 2 severity
per Common Terminology Criteria for Adverse Events Version 4.3.

- Significant cardiovascular impairment: history of CHF greater than New York Heart
Association (NYHA) Class II, unstable angina, MI or stroke within 6 months of the
first dose of study drug, or cardiac arrhythmia requiring medical treatment.

- Uncontrolled hypothyroidism defined as serum TSH higher than 5 mIU/mL while receiving
appropriate thyroid hormone therapy.

- Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR
monitoring, e.g., warfarin or similar agents. Treatment with LMWH and factor X
inhibitors that do not require INR monitoring is permitted. Anti-platelet agents are
prohibited throughout the study.

- Current treatment with any prohibited medications associated with prolongation of QT
interval.

- Received strong inhibitors of CYP2C8 or CYP3A4 or strong inducers of CYP3A4 ≤ 7 days
prior to first dose of lucitanib or have on-going requirements for these medications.

- Received bevacizumab < 3 months prior to first dose of lucitanib.

- Major surgery (not including placement of central lines) within 3 weeks prior to study
or planned surgery during the course of this study.

- Subjects with breast or lung cancer who are eligible for other clinical trials of
lucitanib open at their institution are not eligible for this trial.