Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Non-small Cell Lung Cancer Patients With EGFR Mutation.

Inclusion criteria:

- Histologically documented, locally advanced or recurrent (stage IIIB who are not
eligible for combined modality treatment) or metastatic (Stage IV) NSCLC

- Locally documented EGFR mutation L858R and/or ex19del, or a characterized de novo EGFR
T790M mutation (or other rare activating mutations that confer sensitivity to 1st and
2nd generation EGFR inhibitors (e.g. L861Q, G719X, S768I)

- Presence of at least one measurable lesion according to RECIST v.1.1

- ECOG performance status ≤1

- Patients must be screened for HBV. Patients who are either HBsAg positive or HBV-DNA
positive must be willing and able to take antiviral therapy 1-2 weeks prior to 1st
dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after
the last dose of EGF816.

- Patients must be screened for HCV. Patients must have negative hepatitis C antibody
(HCV Ab) or are HCV Ab positive but with an undetectable level of HCV-RNA. Note:
patients with detectable HCV-RNA are not eligible for the study.

- Phase Ib only: documented progression of disease according to RECIST v1.1 while on
continuous treatment with EGFR TKI (e.g.: erlotinib, gefitinib or afatinib).

- Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI
resistant) only: Patients demonstrated a documented clinical benefit (CR (any
duration), PR (any duration), or SD for at least 6 months) on prior EGFR TKI (e.g.
erlotinib, gefitinib or afatinib, and subsequently demonstrated progression according
to RECIST v1.1.

- Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI
naïve) only: Advanced NSCLC patients who have not been previously treated with any
therapy known to inhibit EGFR and harbor de novo T790M mutation .

- Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic) only:
patients must harbor an EGFR activating mutation and must be naïve from any line of
systemic antineoplastic therapy in the advanced setting.

- Phase II Group 4 (EGFRmut, any T790M, any c-MET, 1L (treatment-naïve), 2//3L
antineoplastic): All patients must harbor an EGFR activating mutation and 2/3L
patients must have failed (defined as intolerance to treatment or documented disease
progression) a maximum of 2 prior lines of antineoplastic therapy in the advanced
setting

Exclusion Criteria:

- Phase Ib:

- More than one previous treatment line with erlotinib, gefitinib or afatinib

- Previous treatment with any investigational agent known to inhibit EGFR (mutant
or wild-type)

- Patients who have received more than three prior lines of antineoplastic
therapies (including EGFR TKI) in advanced setting.

- Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI
resistant):

- More than 3 prior lines of systemic antineoplastic therapies (including EGFR TKI)
in the advanced setting

- More than 1 previous treatment line with 1st or 2nd generation EGFR TKI (e.g.
erlotinib, gefitinib, afatinib) in the advanced setting

- Previous treatment with an investigational or marketed 3rd generation EGFR TKI
(e.g. AZD9291, CO-1686, ASP8273, EGF816)

- Previous treatment with an investigational or marketed agent known to inhibit
EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).

- Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI
naïve):

- More than two previous treatment lines of systemic antineoplastic therapies in
the advanced setting

- Previous treatment with an investigational or marketed agent that inhibits EGFR.
EGFR inhibitors include (but not limited to) all generations of EGFR TKI
(e.g.erlotinib, gefitinib, afatinib, AZD9291, CO-1686, ASP8273, EGF816) or other
anti-EGFR or EGFR monoclonal antibody therapy or dual TKI inhibitors.

- Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic):

- De novo EGFR T790M mutation identified by central assessment

- Previous treatment with any systemic antineoplastic therapy in the advanced
setting (NSCLC stage IIIB or IV. Patients who received only one cycle of
antineoplastic therapy in the advanced setting are allowed).

- Phase II Group 4 (EGFRmut, any T790M, any c-MET, 1/3L antineoplastic):

- More than 2 prior lines of systemic antineoplastic therapies in the advanced
setting

- Previous treatment with an investigational or marketed 3rd generation EGFR TKI
(e.g. AZD9291, CO-1686, ASP8273, EGF816)

- Previous treatment with an investigational or marketed agent known to inhibit
EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor).

- Previous treatment with a c-MET inhibitor or HGF-targeting therapy.

- Patients with symptomatic brain metastases.

- Presence or History of another malignancy. Exception: Patients who have been
disease-free for 3 years, or patients with a history of adequately treated in-situ
carcinoma of the uterine cervix, completely resected basal or squamous cell carcinoma,
non-melanomatous cancer of skin, history of stage IA melanoma that has been cured, are
eligible.

- Undergone a bone marrow or solid organ transplant.

- Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not
mandatory)

- Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use
at the time of study entry except for control of brain metastases, topical
applications, inhaled sprays, eye drops or local injections

- Patients with clinically significant, uncontrolled cardiovascular disease

- Presence or history of interstitial lung disease or interstitial pneumonitis

- Patients have not recovered from all toxicities related to prior anticancer therapies
to grade ≤1 (CTCAE v 4.03)

- Patients have out of range laboratory values defined as

1. Absolute Neutrophil Count (ANC) <1.5 x 109/L (1.5x103/µL)

2. Hemoglobin (Hb) <9 g/dL (90g/L)

3. Platelets (PLT) <75 x 109/L (75x103/µL)

4. Total bilirubin >1.5 x upper limit of normal (ULN).

5. AST and/or ALT >3 x ULN

6. Patients with liver metastasis may not be included if AST and/or ALT >5 xULN

7. Alkaline phosphatase (ALP) >5 xULN

8. Calculated creatinine clearance < 45mL/min (0.75 mL/sec)using Cockroft-Gault
formula

9. Asymptomatic serum amylase or lipase > Grade 2

10. Serum amylase or serum lipase CTCAE grade ≥ 1 with signs and/or symptoms
suggesting pancreatitis or pancreatic injury (e.g. elevated P-amylase, abnormal
imaging findings of pancreas, etc)

- Patients have the following laboratory values outside of the laboratory normal limits
or cannot be corrected to within normal limits with supplements during screening:
Potassium, Magnesium, Phosphorus, Total calcium (corrected for serum albumin)

Other protocol-defined inclusion/exclusion criteria may apply.