Patient case: 64-year-old female with melanoma; genetic feature: BRAF (E586K)

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

Summary: This open-label, multi-center Phase 1/2 study will assess the safety, pharmacokinetics, and pharmacodynamics of escalating doses of BVD-523 in patients with advanced malignancies. The study also seeks to demonstrate target modulation and early signs of clinical response in select patient populations.

Detailed description: The study is being performed to assess the safety and tolerability of BVD-523
  In Part 1 of the study, an accelerated dose escalation plan will be used to establish dose limiting toxicities, maximum tolerated dose, and the recommended Phase 2 dose.
  In Part 2 of the study, additional patients with particular tumor types and/or cancers harboring specific genetic mutations will be recruited for treatment at the Recommended Phase 2 Dose. Patients may also be assessed pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.

Eligibility: 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

Relevance to patient case: possibly relevant