Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies

Inclusion Criteria:

* Patients with metastatic or advanced-stage malignant tumor. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease
* ECOG score of 0 or 1
* Predicted life expectancy of ≥ 3 months
* Adequate bone marrow, liver and renal function renal function
* Adequate cardiac function
* For women: Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal, or compliant with a contraceptive regimen during and for 3 months after the treatment period
* For men: Must be surgically sterile, or compliant with a contraceptive regimen during and for 3 months after the treatment period
* For Part 2 of the Study only, patients must have measurable disease by RECIST 1.1 and be in one of the the groups below. Patients in groups 1, 2, 4, 5 and 6 may not have been previously treated with BRAF and/or MEK inhibitors

  * Group 1: Patients with BRAF mutated cancer, except those with colorectal or non-small cell lung cancers
  * Group 2: Patients with BRAF mutated colorectal cancer
  * Group 3: Patients with BRAF mutated melanoma who have progressed on, or are refractory to BRAF and/or MEK inhibitors
  * Group 4: Patients with NRAS mutated melanoma
  * Group 5: Patients with MEK mutated cancer
  * Group 6: Patients with BRAF mutated non-small cell lung cancer
  * Group 7: Patients with ERK mutated cancer

Exclusion Criteria:

* Gastrointestinal condition which could impair absorption of study medication
* Uncontrolled or severe intercurrent medical condition
* Known uncontrolled brain metastases. Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants
* Any cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days or 5 half-lives, whichever is shorter
* Major surgery within 4 weeks prior to first dose
* Any use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of BVD-523.
* Pregnant or breast-feeding women
* Any evidence of serious active infections
* Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study
* A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
* Concurrent therapy with any other investigational agent
* Concomitant malignancies or previous malignancies with less than 2 years disease-free interval at the time of enrollment