1. Dose Escalation Phase: Histologic diagnosis of GBM or gliosarcoma. Progressed during
or after standard 1st-line therapy for GBM. Patients scheduled to undergo a repeat
primary surgical resection are also eligible. Measurable disease as measured by RANO
(Response Assessment in Neuro-Oncology) criteria
2. Dose Expansion Phase:
Cohort A: Histologic diagnosis of GBM or gliosarcoma. Progressed during or after
standard 1st-line therapy for GBM. Patients scheduled to undergo a repeat primary
surgical resection are also eligible. Measurable disease as measured by RANO criteria
Cohort B: Metastatic colorectal cancer (mCRC) patients after progression on
2nd-line therapy for advanced disease. Measurable disease as measured by RECIST
(Response Evaluation Criteria in Solid Tumors) v1.1
Cohort C: Metastatic renal cell carcinoma (mRCC) (with clear cell component) patients
after progression on 1st-line therapy for advanced disease. Measurable disease as
measured by RECIST v 1.1
At least 5 patients in each of the above 3 cohorts must have alteration of MET [as
assessed by FISH (c-MET/centromere ratio 2, or c-MET gene copy number 5) or RT-PCR
or Met IHC score of 2-3+ or a mutation].
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2 or
Karnofsky Performance Scale (KPS) >70%
4. Adequate hematologic, renal and liver function
5. Life expectancy 3 months
6. Availability of archived tumor samples and/or willingness to provide tissue samples
if resection is done. (Fresh tissue biopsy is not required if archival tissue is not
1. Prior treatment with bevacizumab or any other VEGF or VEGFR inhibitors for GBM
patients; prior treatment with bevacizumab for mRCC patients. (Prior treatment with
bevacizumab is permitted for mCRC patients)
2. Uncontrolled seizures (Patients with a history of seizures are eligible if they are
currently without seizures on a stable dose of anti-epileptic drugs for 14 days prior
3. History of uncontrolled hereditary or acquired bleeding or thrombotic disorders.
4. A serious non healing wound, ulcer, or bone fracture 28 days to the start of
5. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
administered 28 days or limited field radiation for palliation 7 days prior to
starting study drug or has not recovered from side effects of such therapy.
6. Leptomeningeal metastases or spinal cord compression due to disease. (mRCC and mCRC
patients with stable treated metastases will be allowed to enroll.)
7. Women of child-bearing potential.
8. Receiving drugs known to be strong inhibitors or inducers of CYP3A4 and cannot be
discontinued 7 days prior to the start of INC280 treatment and during the course of
the study, or medications that are known CYP3A4, CYP1A2, CYP2C8, CYP2C9 or CYP2C19
substrates with narrow therapeutic index, and cannot be discontinued during the
course of the study.
9. Treatment with proton pump inhibitors within three days prior to study entry.
10. Cardiac disease currently or less than 6 months from baseline screening
11. Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg
or diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels
must have their blood pressure (BP) controlled with medication prior to starting
12. Currently receiving treatment with therapeutic doses of warfarin sodium. Low
molecular weight heparin is allowed.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both