On December 12, 2022 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported positive updated clinical data from the ongoing open label Phase 1a dose escalation study of emavusertib (CA-4948), a novel, small molecule IRAK-4 inhibitor, as a monotherapy in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or high risk myelodysplastic syndromes (hrMDS) in both targeted and non-targeted populations (Press release, Curis, DEC 12, 2022, View Source [SID1234625102]). Patients in a targeted population are those with disease harboring U2AF1, SF3B1 (collectively "spliceosome") or FLT3 mutations. The company also announced positive initial data of emavusertib in combination with venetoclax in patients with AML or hrMDS that enrolled in the combination phase (Phase 1b) of the TakeAim Leukemia study prior to the partial clinical hold placed in April 2022.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We have nearly doubled the size of the targeted patient data set, and continue to see consistent and deep anticancer activity, including additional objective responses. We believe these data suggest a favorable anti-cancer activity compared to therapies currently available for these patients. We are also encouraged by the initial combination data," said James Dentzer, President and Chief Executive Officer of Curis.
As of October 12, 2022, the total monotherapy data to date represents 24 response evaluable patients with a targeted mutation and 34 response evaluable patients without a targeted mutation. This represents 11 additional patients treated in targeted monotherapy populations and 13 additional patients in the non-targeted monotherapy population. In addition to the monotherapy data, there are 4 patients with AML/hrMDS who have been treated with emavusertib in combination with venetoclax.
In Expanded Data Set, Findings Support Earlier Data Presented in June 2021 and January 2022
Previous data presented by Curis highlighted preliminary efficacy data of emavusertib in R/R AML/MDS patients whose disease is characterized by spliceosome or FLT3 mutation. It is this genetically-defined subset of AML/MDS that is specifically targeted by emavusertib and which we believe, represents the patients most likely to benefit from treatment with emavusertib in monotherapy. Today’s clinical data update provides an expanded data set for this genetically-defined patient population.
In targeted AML patient monotherapy populations key findings included:
Patients with a FLT3 mutation had a CR (complete remission) rate of 29% (2 of 7 patients);
In addition to the 2 patients who achieved CRs, a 3rd patient achieved MLFS (morphologic leukemia-free state), and a 4th patient with gilteritinib-refractory disease achieved near normalization of blast count and complete loss of detectable FLT3 clone
Patients with a spliceosome mutation had CR/CRh rate of 22% (2 of 9 patients)
In targeted hrMDS patient monotherapy populations key findings included:
ORR (objective response rate) of 45% (5 of 11 patients)
All 5 responses achieved a marrow CR (mCR)
In combination AML/hrMDS patient populations key findings included:
ORR of 50% (2 of 4 patients)
Both responses achieved mCR
These data continue to confirm the earlier data that emavusertib provides favorable anti-cancer activity in AML and hrMDS patients with a spliceosome and/or FLT3 mutation. Further, anti-cancer activity in non-targeted patients as well as in combination with venetoclax suggest potential for incremental efficacy in combination with existing therapies. We are continuing to enroll patients at the 200mg dose level and plan to discuss with the U.S. Food and Drug Administration (FDA) a recommended phase 2 dose in mid-2023.
Conference Call Information
Curis management will host a conference call today, December 12, 2022 at 10:00 a.m. ET, to discuss the results with Dr. Eric Winer, Clinical Investigator at the Dana-Farber Cancer Institute. To access the live call, please dial (888) 346-6389 from the United States or (412) 317-5252 from other locations, shortly before 10:00 a.m. ET. A live webcast will be available under "Events & Presentations" in the Investors section of the Company’s website at www.curis.com. A replay of the webcast will be available on the Curis website shortly after completion of the call.
About emavusertib (CA-4948)
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-κB 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.
About TakeAim Studies
TakeAim Leukemia Study (NCT04278768) – This study is only enrolling in the monotherapy dose finding phase (phase 1a) of the study. The partial hold remains in place for the combination therapy phase (phase 1b) and expansion phase (phase 2a) of the study.
TakeAim Lymphoma Study (NCT03328078) – This study is open for enrollment.