New Expanded Access Program for MAPK-Pathway Altered Cancers

Musella Foundation collaborator, xCures, recently announced the opening of an IND for an intermediate Expanded Access Program for the investigational ERK inhibitor ulixertinib (BVD-523). Ulixertinib is a first-in-class small-molecule inhibitor of extracellular signal-regulated kinase (ERK) family kinases (ERK1 and ERK2) that is being developed as a novel anti-cancer drug. ERK kinases are downstream components of the mitogen-activated protein kinase (MAPK) signaling cascade. Ulixertinib has demonstrated promising early efficacy for patients with tumors harboring alterations in the MAPK pathway, including atypical (non-V600) BRAF alterations, for which there are currently no approved targeted agents.

While a phase I study of ulixertinib in advanced solid malignancies had shown two central nervous system responses, a window-of-opportunity trial is currently being conducted to study the drug's ability to cross the blood brain barrier. A SNO 2024 abstract on the window-of-opportunity trial revealed that at least three GBM patients have been treated with ulixertinib under the EAP; one NRAS GBM patient was on study for 15 weeks, one BRAFV600E GBM patient was on study for 18 weeks, and one NF1 GBM patient was on study for 33 weeks (still ongoing). A separate Phase 2 study of ulixertinib for patients with advanced malignancies harboring MEK or atypical BRAF alterations was terminated due to enrollment challenges; however, results posted on clinicaltrials.gov showed there were 0 objective responses amongst the 77 enrolled patients, and median progression free survival was only 1.5 months. Researchers are also conducting preclinical studies to understand whether combination therapies utilizing MAPK inhibitors, like ulixertinib, may improve efficacy in high grade glioma. Ulixertinib is being developed by BioMed Valley Discoveries (BVD), a clinical stage biotechnology company, as a treatment for patients with MAPK pathway altered solid tumors, including those with activating mutations in KRAS, NRAS, HRAS, BRAF, MEK, and/or ERK.

Expanded access, which is often called "compassionate use," is the use of an unapproved drug for treatment of patients with serious or life-threatening illnesses outside of a clinical trial. Expanded access is subject to oversight from the US FDA in accordance with the regulations outlined in 21 CFR 312.305. In this case, xCures is sponsoring the program and making ulixertinib available to physicians for the treatment of eligible cancer patients who are aged 12 or older. The EAP is open across the United States to adolescent and adult cancer patients who cannot access an open clinical trial of ulixertinib, which is currently in phase 2 development. xCures uses a patient-centric approach to generate real-world data from expanded access programs in order to reduce the burden on patients and clinicians. This approach can help meet the requirement to provide a case report to health authorities by using real-world data.

Interested patients and physicians can learn more at the xCures Web site: https://enroll.xcures.com/uli-eap/