Patient case: 35-year-old female with Breast cancer. Genetic variant: NRAS Amplification. Other conditions: None.

Clinical trial: Study of Safety and Efficacy of INC280 and Cetuximab, in Adult c-MET Positive mCRC and HNSCC Patients After Progression on Cetuximab or Panitumumab Therapy

Summary: This is an open-label, phase Ib, multicenter clinical trial to determine the MTD/RDE of the orally administered c-MET inhibitor INC280 in combination with cetuximab. This combination will be explored in c-MET positive mCRC and HNSCC patients whose disease progressed on cetuximab or panitumumab treatment. The dose escalation part will be guided by a Bayesian Logistic Regression Model with overdose control. At MTD/RDE, additional mCRC and HNSCC patients who have progressed on cetuximab or panitumumab treatment will be enrolled in two expansion groups to further assess the anti-tumor activity and the safety and tolerability of the combination of INC280 and cetuximab. Patients will receive INC280 on a continuous bid dosing regimen and cetuximab every week. A treatment cycle is defined as 28 days with no scheduled break between cycles.


Eligibility: Inclusion Criteria:
  -  Male or female aged ≥ 18 years
  -  Metastatic colorectal cancer or head and neck squamous cell carcinoma
  -  c-MET positive (defined by c-MET IHC intensity score +2 in ≥ 50% of tumor cells and MET gene copy number ≥ 5 by FISH or IHC intensity score +3 in ≥ 50% of tumor cells) and K/NRAS WT status for mCRC patients only
  -  At least one previous line of treatment for the metastatic disease and the last treatment must have included cetuximab or panitumumab. Documentation of clinical benefit and subsequent progression on cetuximab or panitumumab as the most recent line of treatment is required for patients in the expansion part
  -  Measurable disease as per RECIST v1.1
  -  ECOG performance status ≤ 2
  Exclusion Criteria:
  -  Prior treatment with c-MET/HGF inhibitors
  -  History of severe reactions to cetuximab and/or panitumumab (except for G3 rash and G3 hypomagnesaemia)
  -  History of acute or chronic pancreatitis
  -  Active bleeding within 4 weeks prior to screening visit
  -  Symptomatic brain metastases
  -  Feeding tube dependence
  -  Not adequate hematologic, renal and hepatic function
  Other protocol-defined inclusion/exclusion criteria may apply NVS Definition: List only the main study specific inclusion/exclusion criteria that patients will understand.
  Note: DO NOT cut/paste directly from the protocol.
  Do not include age and gender as part of this field. Age and gender are indicated in the 2 fields below.
  Always include statement "Other protocol-defined inclusion/exclusion criteria may apply" at the end of this section.
  Examples:
  Inclusion criteria:
  Patients within 7- 42 days of an acute myocardial infarction associated with left ventricular systolic dysfunction Qualifying Echocardiogram at Visit 1
  Exclusion criteria:
  Presence of clinically overt heart failure Percutaneous coronary intervention (PCI) less than 24 hours before randomization previous treatment with aliskiren
  Other protocol-defined inclusion/exclusion criteria may apply.

Relevance to patient case: not relevant