NCT04488003

Study of Ulixertinib for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations

A Two-Part, Phase II, Multi-center Study of the ERK Inhibitor Ulixertinib (BVD-523) for Patients With Advanced Malignancies Harboring MEK or Atypical BRAF Alterations

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 104 (actual)
• Sponsor: BioMed Valley Discoveries, Inc · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This BVD-523-ABC study builds on the safety and clinical activity experience of previous studies that have evaluated ulixertinib as a novel targeted cancer treatment in cohorts of patients with specific genetic alterations and tumor histologies that result in aberrant MAPK pathway signaling. Early clinical data have demonstrated anti-tumor activity with ulixertinib treatment and have identified specific groups of patients for whom additional development is warranted.

Detailed description

This multi-center, phase II study will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib (BVD-523) in patients with advanced malignancies. Part A (tumor histology agnostic) will be open label and enroll patients to one of six groups based on their tumor alteration. Targeted enrollment per group was 38 patients with a total targeted enrollment of 228 patients. Actual enrollment was total of 104 patients with 77 patients allocated to treatment. * Group 1: Patients with tumors, other than colorectal cancer (CRC), having a BRAF alteration that results in an amino acid change at positions G469, L485, or L597. * Group 2: Patients with tumors, other than CRC, having a defined Class 2 BRAF alteration (see Appendix 2 of protocol). * Group 3: Patients with tumors, other than CRC, having an atypical BRAF alteration (non V600) that is not specified in Group 1 or Group 2. * Group 4: Patients with CRC having any atypical BRAF alteration. * Group 5: Patients with tumors, other than CRC, harboring alterations in MEK1/2. * Group 6: Patients with CRC harboring alterations in MEK1/2. Part B (tumor histology specific) will randomly enroll patients with one of up to three specified tumor histologies to receive either ulixertinib or the physician's choice of treatment in a 2:1 ratio. Tumors must harbor a specified MEK or atypical BRAF alteration. If a patient progresses on physician's choice of treatment, crossover to the ulixertinib arm is permitted.The specific histologies to be included in this part will be selected based on available data and discussion with the clinical investigators, the medical monitor, and the sponsor. Total enrollment was targeted to approximately 80-100 patients per histology with up to three histologies included; however, the study was terminated prior to any patients enrolling in Part B.

Conditions

• Advanced Solid Tumor
• BRAF Gene Mutation
• BRAF Gene Alteration
• MEK Mutation
• MEK Alteration
• MAP2K1 Gene Mutation
• MAP2K1 Gene Alteration
• MAP2K2 Gene Mutation
• MAP2K2 Gene Alteration

Interventions

Type	Name	Description
DRUG	Ulixertinib	Oral, 600 mg, twice daily, for 28-days in each treatment cycle
DRUG	Physician's Choice	Physician's choice will be restricted to two approved (not off-label) treatments for each tumor histology (agents targeting BRAF or MEK kinases and experimental agents are not permitted as physician choice)).

Timeline

• Start date: 2021-01-07
• Primary completion: 2023-02-15
• Completion: 2023-05-23
• First posted: 2020-07-27
• Last updated: 2024-06-04
• Results posted: 2024-06-04

Locations

22 sites across 1 country: United States

Regulatory

• FDA-regulated drug study