A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor

Inclusion Criteria

• Written informed consent must be obtained prior to any screening procedures.
• Age ≥ 18 years
• Histologically or cytologically confirmed non-small cell lung cancer, advanced, recurrent, or metastatic
• MET exon 14 skipping alteration by molecular testing (local testing is accepted for eligibility; all patients will have confirmation by NGS-rearrangement assay at MGH but this result is not necessary for eligibility; local molecular pathology result will suffice). This testing can be from any archival or fresh sample.
• Must have received prior platinum containing chemotherapy for advanced/metastatic non-small cell lung cancer, or have refused or be ineligible for such therapy. Prior neoadjuvant/adjuvant platinum containing chemotherapy will count has having received prior platinum, provided that disease recurred within 6 months of completion of neoadjuvant/adjuvant therapy.
• EGFR and ALK status must be known in all patients with adenocarcinoma histology. Patients with activating EGFR mutations or ALK translocations are excluded from this study, unless disease has progressed on all available, approved therapies targeting these alterations.
• At least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.
• Must have received prior MET inhibitor as their immediately preceding therapy. There are no limits to the number of lines of prior therapy as long as prior MET inhibitor is the most recent therapy.
• Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
• Patients must have adequate organ function including the following laboratory values at the screening visit:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support
• Platelets ≥ 75 x 109/L
• Hemoglobin (Hgb) > 9 g/dL
• Calculated creatinine clearance (using Cockcroft-Gault formula) > 45 mL/min
• Total bilirubin ≤ 1.5 x ULN, except for patients with Gilbert's syndrome, who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
• Aspartate transaminase (AST) ≤ 3 x ULN, except for patients with liver metastasis, who are included if AST ≤ 5 x ULN
• Alanine transaminase (ALT) ≤ 3 x ULN, except for patients with liver metastasis, who are only included if ALT ≤ 5 x ULN
• Alkaline phosphatase (ALP) ≤ 5.0 x ULN
• Asymptomatic serum amylase ≤ grade 2. Patients with grade 1 or grade 2 serum amylase at the beginning of the study must be confirmed to have no signs and/or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated P-amylase, abnormal imaging findings of pancreas, etc.)
• Serum lipase ≤ ULN
• Patients must have the following laboratory values within the laboratory normal limits or corrected to within normal limits with supplements during screening:
• Potassium
• Magnesium
• Phosphorus
• Total calcium (corrected for serum albumin)
• ECOG performance status (PS) of 0 or 1
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria

• Patients with known hypersensitivity to any of the excipients of INC280 (crospovidone, mannitol, microcrystalline cellulose, povidone, sodium lauryl sulfate, magnesium stearate, colloidal silicon dioxide, and various coating premixes).
• Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms
• Presence or history of carcinomatous meningitis
• Presence or history of a malignant disease other than disease to be treated in current protocol that has been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include the following: completely resected basal cell and squamous cell