Curis, Inc. announced the presentation of encouraging clinical data from both the TakeAim Lymphoma and TakeAim Leukemia studies at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting currently taking place in Chicago and online until June 7, 2022. The TakeAim Lymphoma study is a Phase 1/2 open-label, dose escalation, dose expansion clinical trial investigating emavusertib as monotherapy and in combination with ibrutinib in patients with R/R hematologic malignancies, such as non-Hodgkins's lymphoma and other B cell malignancies. The poster presentation (#7575) made by Dr. Grzegorz Nowakowski, Division of Hematology, Mayo Clinic-Minnesota, at ASCO includes clinical data from a May 6, 2022 data cutoff, on 13 patients who received the combination, 9 of whom had post-baseline response assessments and were evaluable for response. Key findings in patients treated with the combination included: The combination appeared to be well tolerated No dose-limiting toxicities (DLTs) at 200mg of emavusertib; 2 DLTs observed at 300mg (stomatitis and syncope) 8 of 9 evaluable patients experienced reduction in tumor burden, including: 2 complete responses (CR) (primary CNS lymphoma and mantle cell lymphoma) 2 partial responses (PR) (chronic lymphocytic leukemia and mantle cell lymphoma) One of the CRs was in a patient who had received prior treatment with ibrutinib, suggesting that the combination may be able to overcome ibrutinib resistance Next steps for the TakeAim Lymphoma study include further dose expansion in order to determine the Recommended Phase 2 Dose for the combination. Emavusertib is an IRAK4 kinase inhibitor and IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, which are frequently dysregulated in patients with cancer. TLRs and the IL-1R family signal through the adaptor protein MYD88, which results in the assembly and activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression mediated by the NF-?B protein complex. Additionally, third parties have recently discovered that the long form of IRAK4 (IRAK4-L) is oncogenic and preferentially expressed in over half of patients with AML and MDS. The overexpression of IRAK4-L is believed to be driven by a variety of factors, including specific spliceosome mutation such as SF3B1 and U2AF1. In addition to inhibiting IRAK4, emavusertib was also designed to inhibit FLT3, a known oncologic driver, which may provide additional benefit in patients with AML and MDS.
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