Phase 1/2 Dose-Escalation, Safety, PK & PD Study of BVD-523, an ERK 1/2 Inhibitor, in Patients With Advanced Malignancies

U.S. FDA Resources

Estimated Enrollment:	120
Study Start Date:	March 2013
Estimated Study Completion Date:	March 2015
Estimated Primary Completion Date:	March 2015 (Final data collection date for primary outcome measure)

Detailed Description:

Inclusion Criteria:

• Patients with metastatic or advanced-stage malignant tumor, confirmed histologically, for whom no therapy exists that would be curative. Patients may have received up to 2 prior lines of chemotherapy for their metastatic disease.
• ECOG performance status of 0 or 1
• Predicted life expectancy of ≥ 3 months

• Adequate bone marrow, liver and renal function renal function as assessed by the following laboratory requirements:

  1. creatinine ≤ 1.5 times ULN (upper limit of normal)] and/or GFR of ≥ 50mL/min
  2. total bilirubin ≤ 1.5 x UNL; AST (aspartate transaminase) and/or ALT (alanine transaminase) ≤ 3x UNL or ≤ 5 x UNL if due to liver involvement by tumor
  3. hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x 10 cells/L; absolute neutrophil count ≥ 1.5 x 109 cells/L
• Adequate cardiac function, e.g. [left ventricular ejection fraction (LVEF) of > 50%; corrected QT interval (QTc) < 470 ms]
• 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 following 4 groups:

  1. Patients with BRAF mutated melanoma; not previously treated with inhibitors of BRAF, MEK, or ERK
  2. Patients with BRAF mutated melanoma who have progressed while being treated with BRAF inhibitors.
  3. Patients with BRAF mutated non-melanoma; not previously treated with inhibitors of BRAF, MEK, or ERK
  4. Patients with RAS mutated advanced malignancy; not previously treated with inhibitors of BRAF, MEK, or ERK

Exclusion Criteria:

• Gastrointestinal (GI) 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, with no dose change in the previous 4 weeks, can be allowed
• 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. A minimum of 10 days between termination of the investigational drug and administration of BVD-523 is required. In addition, any drug- related toxicity except alopecia should have recovered to Grade 1 or less
• 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 (RVO) or central serous retinopathy (CSR)
• Concurrent therapy with any other investigational agent
• Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, or CYP3A4, or strong inducers of CYP3A4.

BioMed Valley Discoveries, Inc