Phase 1 Trial Demonstrates Encouraging Clinical Benefit and Promising Safety Profile of Pacritinib for the Prevention of Graft-Versus-Host Disease Published in Clinical Cancer Research
The Phase 1 portion of the trial (NCT02891603) evaluated the safety of pacritinib when administered with sirolimus plus low-dose tacrolimus after allogeneic hematopoietic cell transplantation (alloHCT). A 3+3 dose escalation design identified PAC 100 mg twice a day as the minimum biologically active and well-tolerated dose for further study. At this dose, one out of six study participants treated with the investigational regimen had Grade 2-4 acute GVHD. Chronic GVHD was rare, with only two participants developing mild disease per
The new manuscript reports that dual JAK2/mTOR inhibition suppresses pathogenic Th1 and Th17 cells, enhances the potency of immunosuppressive regulatory T cells (Tregs), and maintains natural killer cells and CD8+ cytotoxic T lymphocytes required for graft-versus-leukemia. Importantly, PAC/SIR/TAC was observed to preserve donor cytomegalovirus (CMV) immunity, permit timely engraftment, and avoid cytopenias observed with nonselective JAK inhibitors.
"The PAC/SIR/TAC regimen provides concurrent inhibition of JAK2 and mTOR, effectively suppressing donor T cell costimulation and IL-6 signal transduction implicated in acute GVHD, while sparing STAT5 activation critical for immune tolerance and donor anti-leukemia immunity," said
"This Phase 1 clinical trial is the first study to demonstrate that combining pacritinib, a selective JAK2 inhibitor, with sirolimus-based GVHD prophylaxis may produce lower rates of acute GVHD compared to the reported rates for sirolimus and tacrolimus alone," said Adam.
Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, IRAK1, and CSF1R. The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development, as well as inflammatory cytokine expression and immune responses. Mutations in these kinases have been shown to be directly related to the development of a variety of blood-related cancers, including myeloproliferative neoplasms, leukemia, and lymphoma. In addition to myelofibrosis, the kinase profile of pacritinib suggests its potential therapeutic utility in conditions such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and chronic lymphocytic leukemia (CLL), due to its inhibition of c-fms, IRAK1, JAK2 and FLT3.
About CTI BioPharma Corp.
We are a biopharmaceutical company focused on the acquisition, development, and commercialization of novel targeted therapies for blood-related cancers that offer a unique benefit to patients and their healthcare providers. We concentrate our efforts on treatments that target blood-related cancers where there is an unmet medical need. In particular, we are focused on evaluating pacritinib, our sole product candidate currently in active late-stage development, for the treatment of adult patients with myelofibrosis. In addition, we have recently started developing pacritinib for use in hospitalized patients with severe COVID-19, in response to the COVID-19 pandemic. We are headquartered in
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The
CTI BioPharma Forward-Looking Statements
Statements included in this press release that are not historical in nature are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are based on current assumptions that involve risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from those expressed or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: our ability to successfully demonstrate the safety and efficacy of pacritinib in various indications across multiple clinical trials; and those risks more fully discussed in the section entitled "Risk Factors" in our Annual Report on Form 10-K for the year ended
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