A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer

• INCLUSION CRITERIA

2.1.1.1 Patients must have histologically or cytologically confirmed papillary Renal Cell Cancer (RCC).

• Patients with bilateral multifocal disease can have tumors localized to the kidney or have metastatic disease
• Patients with sporadic papillary RCC (but without multifocal disease) should have advanced disease that is considered unresectable

2.1.1.2 Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions). Nodal lesions must be 15mm by computed tomography (CT) scan or magnetic resonance imaging (MRI). Non nodal lesions must be >10 mm with CT scan or MRI.

2.1.1.3 Patients must have normal organ and marrow function as defined below:

• Hemoglobin > 9 g/dL (SI Units: 90 g/L)
• Platelet count greater than or equal to 75 x 10 (9)/L
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10(9)/L without growth factor support
• Total bilirubin less than or equal to 2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 x upper limit of normal (ULN)
• Serum creatinine less than or equal to 1.5 x ULN
• Asymptomatic serum amylase less than or equal to 2 x ULN; patients with > ULN but less than or equal to 2 x ULN serum amylase at study start must be confirmed to have no signs and/or symptoms suggestion pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
• Serum lipase less than or equal to ULN
• Fasting serum triglyceride level less than or equal to 500 mg/dL

2.1.1.4 Patients may have had no more than 3 prior lines of systemic therapy. Prior therapy with a mesenchymal epithelial transition (MET) inhibitor is allowed as long as the patient has not had progressive disease while receiving the agent

2.1.1.5 Patient must be able to swallow and retain oral medication

2.1.1.6 Age greater than or equal to18 years.

2.1.1.7 Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.

2.1.1.8 Patients must provide written informed consent prior to any study procedures.

2.1.1.9 Patients must be willing and able to comply with scheduled visits, treatment plan and laboratory tests

EXCLUSION CRITERIA

2.1.2.1 Patients who are receiving any other investigational agents for treatment of their kidney cancer.

2.1.2.2 History of allergic reactions attributed to compounds of similar chemical or biologic composition to Capmatinib (INC280). Excipients in the current formulation include microcrystalline cellulose, mannitol, sodium starch glycolate, magnesium stearate and colloidal silicon dioxide

2.1.2.3 Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or potentially affect the interpretation of study data.

2.1.2.4 Subjects with significant or uncontrolled cardiovascular disease (e.g., uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months prior to starting study treatment or heart attack within 12 months prior to starting study treatment

2.1.2.5 Patients receiving any medications that are known to be strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), or sensitive substrates of CYP3A4, cytochrome P450 1A2 (CYP1A2), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 2C19 (CYP2C19) or P-glycoprotein (P-gp) with a narrow therapeutic index.

2.1.2.6 Symptomatic central nervous system (CNS) metastases that are neurologically unstable or requiring > 5 mg/day of