Phase 1 Study of Type II JAK2 Inhibitor in Myelofibrosis Enrolls First Patient
The study is evaluating AJ1-11095, a novel agent for the treatment of myelofibrosis that did not respond to or relapsed following treatment with a type I JAK2 inhibitor.
Primary myelofibrosis cells in blood flow: © LASZLO - stock.adobe.com
A phase 1 clinical trial (NCT06343805) evaluating AJ1-11095, a first-in-class type II JAK2 inhibitor for the treatment of myelofibrosis, has enrolled its first patient.1
“There continues to be a significant unmet need for [patients with] myelofibrosis who lose or lack response to existing therapies. AJ1-11095 is a promising new therapeutic option for these patients, and we look forward to the clinical results from the phase 1 study,” said John Mascarenhas, MD, professor of medicine, Icahn School of Medicine at Mt. Sinai and director, Center of Excellence in Blood Cancers and Myeloid Disorders at Tisch Cancer Institute, in a press release. Mascarenhas is also the principal investigator of the phase 1 study.
AJ1-11095 is the first JAK2 inhibitor that binds to the type II conformation of the JAK2 kinase compared with other approved JAK2 inhibitors like ruxolitinib (Jakafi) that bind to the type I conformation. In preclinical studies, AJ1-11095 showed improved efficacy compared with type I JAK2 inhibitors and showed significant disease-modifying effects on mutant allele burden and fibrosis.
“We’re excited to announce dosing of the first patient enrolled in our first-in-human study with AJ1-11095” said David Steensma, MD, FACP, chief medical officer of Ajax Therapeutics, in the press release. “As a first-in-class therapy with a unique mechanism of action as a type II inhibitor of JAK2, AJ1-11095 was developed to provide a much-needed new treatment for patients with myeloproliferative neoplasms by offering the potential for improved efficacy compared to existing therapies.”
The phase 1 study is an open-label, multicenter, dose-escalation and -expansion study.2 The primary end points are incidence of adverse events, dose-limiting toxicities, and establishing the maximum tolerated dose (MTD). Secondary end points include clinical response, spleen response, and pharmacokinetics. The dose-escalation study will follow a 3+3 cohort design until the recommended phase 2 dose or MTD is determined.
Patients aged 18 years or older with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis who did not achieve a response on or relapsed following treatment with a type I JAK2 inhibitor are eligible to enroll in the study. Patients must also have DIPSS intermediate-2 or high-risk myelofibrosis with ≤10% blasts, regardless of JAK2 mutation status, and adequate laboratory values.
Exclusion criteria include prior splenectomy, uncontrolled intercurrent illness, chronic active or acute hepatitis B or C infection, and administration of chemotherapy within 4 weeks.
