Abstract
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 (BVD-523-ABC)
Journal of clinical oncology, Vol.40(16_suppl), pp.TPS3172-TPS3172
06/01/2022
DOI: 10.1200/JCO.2022.40.16_suppl.TPS3172
Abstract
TPS3172
Background: Ulixertinib (BVD-523) is a small molecule inhibitor of extracellular signal-regulated kinases 1/2 (ERK1/2) in development as a novel anti-cancer drug. Early clinical data demonstrated anti-tumor activity, especially for patients with tumors harboring atypical BRAF or MEK1/2 alterations (Sullivan et al., Cancer Discov. 2018;8(2):184-195). Atypical BRAF (non-V600) alterations can be categorized according to characteristics of molecular signaling (Class II or III), are seen in approximately 3% of all human cancers, and there are currently no approved therapies for this indication. Similar to atypical BRAF alterations, the incidence of MEK1/2 alterations are rare in human tumors (< 1 %). Preclinical data have demonstrated activity of ulixertinib in MEK mutant models. Ulixertinib has FDA fast-track designation for patients with solid tumors, other than CRC, with specific BRAF mutations (G469A, L485W, or L597Q). Designed with intent to register, the BVD-523-ABC clinical trial will continue evaluation of ulixertinib in patients with tumors harboring any atypical BRAF or MEK1/2 alteration (NCT04488003). Methods: This multi-center, phase II study, will be conducted in two parts and assess the clinical benefit, safety, pharmacokinetics, and pharmacodynamics of ulixertinib in patients with advanced malignancies. Ulixertinib will be administered at the RP2D of 600 mg BID for 28-day treatment cycles. Eligible patients will have locally advanced or metastatic cancer which progressed following standard systemic therapies, or for which the patient is not a candidate or refused systemic therapy. Planned correlative analyses include reverse phase protein array and transcriptomics of tumor tissue. Part A is open-label and tumor agnostic, except for group 4 and 6 (CRC patients only). Patients will enroll into one of six groups based on BRAF (groups 1-4) or MEK1/2 (groups 5-6) tumor alteration (38 patients per group). Overall response rate (ORR) is the primary endpoint for Part A, with secondary endpoints including duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Part B is tumor histology specific. Patients will be randomized to receive either ulixertinib or physician's choice of treatment in a 2:1 ratio. Up to three specified tumor histologies will be defined, guided by available Part A data (n = 80-100 per histology). The primary endpoint of Part B is PFS, and secondary endpoints include OS, ORR, and DOR. This study has enrolled 43 patients of the planned 228 in Part A at the time of abstract submission. Clinical trial information: NCT04488003.
Details
- Title: Subtitle
- 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 (BVD-523-ABC)
- Creators
- Mark E. Burkard - University of Wisconsin Carbone Cancer CenterMeredith McKean - Sarah CannonJordi Rodon Ahnert - The University of Texas MD Anderson Cancer CenterNiharika B. Mettu - Duke Medical CenterJeremy Clifton Jones - Mayo Clinic in FloridaJamal Ghazi Misleh - Medical Oncology Hematology ConsultantsWen Wee Ma - Mayo ClinicKian-Huat Lim - Washington University in St. LouisE. Gabriela Chiorean - Fred Hutch Cancer CenterMichael J. Pishvaian - Johns Hopkins MedicineShirish M. Gadgeel - Henry Ford Health SystemHeidi Ann McKean - Avera HealthBrent Kreider - BioMed Valley Discoveries, Kansas City, MODeb Knoerzer - BioMed Valley Discoveries, Kansas City, MOAnna Groover - BioMed Valley Discoveries, Kansas CityMary Laura Varterasian - Ann Arbor Center for Independent LivingJessica A. Box - BioMed Valley Discoveries, Kansas City, MOCaroline Emery - BioMed-Valley Discoveries, Kansas City, MORyan J. Sullivan - Massachusetts General Hospital
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.40(16_suppl), pp.TPS3172-TPS3172
- DOI
- 10.1200/JCO.2022.40.16_suppl.TPS3172
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 06/01/2022
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984701246202771
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