Phase 2
Completed N=136
Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
Source: ClinicalTrials.gov NCT01781429 ↗Enrolled (actual)
136
Serious AEs
52.6%
Results posted
Mar 2020
Primary outcomePrimary: Determination of Recommended Phase 2 Dose (RP2D) of BVD-523 by Dose-limiting Toxicities (DLT). — 0; 0; 0; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Determination of Recommended Phase 2 Dose (RP2D) of BVD-523 by Dose-limiting Toxicities (DLT). |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Characterization of the Time Versus Plasma Concentration Profiles of BVD-523 and Selected Metabolites. |
NA; 14.9; 100; 133; 216; 765 | — |
| SECONDARY Clinical Evidence of Tumor Response Assessed by Physical or Radiological Exam. |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01781429). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.