Description:
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.
Title
- Brief Title: Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
- Official Title: Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies
Clinical Trial IDs
- ORG STUDY ID:
BVD-523-01
- SECONDARY ID:
BVD-523-01
- NCT ID:
NCT01781429
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| BVD-523 | | BVD-523 |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| BVD-523 | Experimental | | |
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Determination of Recommended Phase 2 Dose (RP2D) of BVD-523 by Dose-limiting Toxicities (DLT). |
| Time Frame: | As indicated by safety and tolerability during study conduct; ~42 months |
| Safety Issue: | |
| Description: | DLT is defined as any BVD-523 related toxicity in the first 21 days of treatment that results in:
≥Grade 4 hematologic toxicity for >1 day;
Grade 3 hematologic toxicity with complications e.g., thrombocytopenia with bleeding;
≥Grade 3 non-hematologic toxicity, except untreated nausea, vomiting, constipation, pain and rash (these become DLTs if the adverse event (AE) persists despite adequate treatment), a doubling of aspartate transaminase (AST)/alanine transaminase (ALT) in patients with grade 2 ALT/AST at baseline;
A treatment interruption exceeding 5 days (or an interruption exceeding 7 days for rash, despite adequate treatment) in Cycle 1 (or inability to begin Cycle 2 for > 7 days) due to BVD-523-related toxicity. |
Secondary Outcome Measures
| Measure: | Characterization of the Time Versus Plasma Concentration Profiles of BVD-523 and Selected Metabolites. |
| Time Frame: | Samples will be collected on day 1 and day 15 of Cycle 1 |
| Safety Issue: | |
| Description: | Data provided is for BVD-523. |
| Measure: | Clinical Evidence of Tumor Response Assessed by Physical or Radiological Exam. |
| Time Frame: | Patients will be evaluated at baseline & at periodic follow-up visits through the time their participation in the study is completion. The best responses presented occurred at different time points for each patient. |
| Safety Issue: | |
| Description: | At enrollment, all study patients had metastatic or advanced-stage malignant tumor for which no curative therapy was known to exist. Patients entering Part 2 additionally had to have measurable disease by RECIST version 1.1. Data shown is best response. |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | BioMed Valley Discoveries, Inc |
Last Updated
March 20, 2020
