Trial of Dasatinib in Subjects With Advanced Cancers Harboring DDR2 Mutation or Inactivating B-RAF Mutation

• Duration of response in responding subjects, by stratum is defined as the time from the first assessment in which response (PR or CR) is documented until the first assessment at which disease progression is documented [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
• Progression-free survival (PFS) rate at 12 weeks of treatment is defined as the proportion of subjects that have no documentation of disease progression at a specified timepoint [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
• Overall PFS distribution in subjects, by stratum is defined as the time from treatment start date to the earliest evidence of disease progression or death. Subjects who do not progress or die will be censored on the date of their last tumor assessment [ Time Frame: Month 24 ] [ Designated as safety issue: No ]
• Safety and tolerability of Dasatinib will be assessed using descriptive summaries of adverse events and laboratory abnormalities [ Time Frame: Month 24 ] [ Designated as safety issue: Yes ]
• Overall survival in subjects, by stratum [ Time Frame: Month 24 ] [ Designated as safety issue: No ]

The purpose of this study is to identify if patients with malignancy harboring a Discoidin Domain Receptor 2 (DDR2) mutation or an inactivating B-RAF mutation will respond to Dasatinib.

• Experimental: Stratum A: Dasatinib
  NSCLC with inactivating B-RAF mutation
  Intervention: Drug: Dasatinib
• Experimental: Stratum C: Dasatinib
  NSCLC of squamous type with DDR2 mutation
  Intervention: Drug: Dasatinib
• Experimental: Stratum D: Dasatinib
  Malignancy of any other histology with DDR2 mutation or inactivating B-RAF mutation, or NSCLC having candidate B-RAF mutation not functionally characterized
  Intervention: Drug: Dasatinib

Inclusion Criteria:

• Diagnosis of advanced malignancy, Non-Small Cell Lung Cancer (NSCLC) only during stage 1 of accrual

• Non-synonymous mutation of B-RAF or DDR2, defined as follows:

  • NSCLC with inactivating B-RAF mutation
  • NSCLC of squamous type with DDR2 mutation
  • Malignancy of other histology with DDR2 mutation or inactivating B-RAF mutation, or NSCLC or melanoma having a B-RAF mutation which is not functionally characterized
• At least one target lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on baseline staging evaluation
• Disease progression after ≥ 1 prior treatment regimen *Exception: Subjects with NSCLC of squamous type may be enrolled in first line, no prior treatment is required

Exclusion Criteria:

• Pleural or pericardial effusion Grade > 1
• QTcF > 470 msec (Grade ≥ 2) or diagnosed congenital long QT syndrome
• Absolute granulocyte count < 1,500/mm3
• Hemoglobin < 10 g/dL
• Platelet count < 75,000/mm3
• Serum calcium < institutional Lower limit of normal (LLN)
• Hypokalemia, hypophosphatemia or hypomagnesemia Grade > 1, despite supplementation
• Creatinine > 3 x institutional Upper Limit of Normal (ULN)
• Total bilirubin > 1.5 x ULN
• Alanine transaminase (ALT) > 3 x ULN