Purpose: Mutations in BRAF at codons other than V600 (non-V600) and BRAF fusions confer dependence on RAF-MEK-ERK pathway. Subprotocol Z1L (EAY131-Z1L) investigated the clinical activity of ulixertinib (ERK1/2 inhibitor) in patients with tumors harboring these alterations. Patients and Methods: In this single-arm study, patients with BRAF non-V600 mutation or BRAF fusion were given ulixertinib orally, at a dose of 600 mg twice daily, continuously for each 28-day cycle until progression or intolerability. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). Results: Among 34 eligible patients, median age was 66.5; 50% were female, 88% were white, 9% black, 3% Asian. ECOG PS 1 in 74% of patients. Median number of prior therapies was 4. Tumor types included multiple gastrointestinal malignancies (n = 16), lung cancer, melanoma (n = 3 each), among others. No patients achieved CR or PR, resulting in ORR = 0%. Stable disease was the best response in 7/26 centrally confirmed cases. Median PFS was 1.7 months (90% CI: 1.1, 2.2), 6-month PFS rate was 5% (90% CI: 0.6%, 17.7%), and median OS was 3.5 months (90% CI: 1.9, 5.4). Twenty patients (57%) had grade 3 toxicities, and one patient (3%) had grade 4 toxicity as their worst toxicity; there were no grade 5 toxicities. Conclusion: Ulixertinib had no demonstrable evidence of clinical activity in this small, heavily pretreated population of patients with tumors harboring BRAF fusions, or with non-V600E, non-V600K BRAF mutations.
Vivek Subbiah, Feng-Min Zhao, R. Kudchadkar et al.· Clinical Cancer Research· 0 citations
Collectively, rare cancers account for approximately 20–25% of all malignancies, and the challenges faced by patients and researchers are consistent across all rare cancer tumor types. Notably, patients encounter challenges in access to clinical trials, access to biomarker testing, and access to expert interpretation of biomarker testing results and subsequent treatment selection. The TargetCancer Foundation TCF-001 TRACK trial is a fully remote, decentralized, patient-driven clinical trial (NCT04504604) that is enrolling patients with any rare cancer (solid tumor or lymphoma, defined as incidence of 6/100,000), and is designed to address these challenges while generating key research data in rare cancers. Enrollment in TRACK is patient initiated, and allows for fully remote consenting and enrollment (via online E-Consent), with no requirement for patients to travel or change their treating physician. Patients receive tissue and blood comprehensive genomic profiling (CGP) at no cost, and a Virtual Molecular Tumor Board, comprised of multidisciplinary members affiliated with a broad national network of institutions from eight states, provides interpretation of CGP reports, along with detailed recommendations for molecularly based treatments. The decentralized model has proven successful in easing participation for patients and ensuring geographic reach, with 230 evaluable patients enrolled across 43 US states and Washington DC, and representing over 60 tumor types, with the highest representation of patients with cholangiocarcinoma, other GI cancers, sarcomas, and brain tumors. However, this model presents significant challenges from an operational perspective, given that each participating patient potentially represents a different treating institution, and outcomes data relies on extraction from requested medical records. Despite these challenges, the TRACK trial provides a scalable decentralized model for equitable access to precision medicine for patients with rare cancers while simultaneously generating data to drive a better understanding of rare cancers that otherwise may have limited treatment options.
Jim Palma, Shumei Kato, Mina Nikanjam, Bicky Thapa, Aditya Shreenivas, Jason Sicklick, Pradip De, Catherine Skefos, Cambree Fillis, Jillian Moran, Hetal Vig, Daniella Olonilua, Mary Oster, Erik Williams, Marcela Johnson, Christian Squatrito, Russell Madison, Richard Huang, Vivek Subbiah, Razelle Kurzrock. On the right TRACK: Operationalizing a national, patient-driven, decentralized trial offering comprehensive genomic profiling and a molecular tumor board for rare cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr IA010.
J. Palma, Shumei Kato, M. Nikanjam et al.· Cancer Research· 0 citations
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