On November 8, 2021 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that the first patient has been dosed in the combination therapy portion of the Phase 1/2 clinical study evaluating CA-4948, a novel, small molecule IRAK4 kinase inhibitor, in acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) (Press release, Curis, NOV 8, 2021, View Source [SID1234594717]).
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 are very pleased to announce the initiation of our Phase 1 combination therapy study of CA-4948, which is an important part of our development strategy to address the broader AML/MDS patient population," said James Dentzer, President and Chief Executive Officer of Curis. "This comes on the heels of the promising initial monotherapy data with CA-4948 in this patient population. Armed with these results and combined with preclinical data highlighting CA-4948’s synergistic antitumor activity when used in combination with azacitidine and venetoclax, and the absence of overlapping dose-limiting toxicity, we are hopeful that this combination portion of the trial will allow us to advance CA-4948 as a promising new treatment for an additional population of patients with AML/MDS."
"Based on CA-4948’s initial efficacy and tolerability in monotherapy, we are looking forward to exploring safety and efficacy for CA-4948 in combination with azacitidine or venetoclax," said Dr. Stefano Tarantolo, M.D., hematologist and oncologist at Nebraska Cancer Specialists and a leading investigator on the study. "We are hopeful that CA-4948 may offer an important new treatment option, as many of these patients are ineligible for intensive chemotherapy and face an extremely poor prognosis."
About the CA-4948 Phase 1/2 Study in Patients with AML/MDS
The Phase 1/2 study was expanded to include both a monotherapy dose expansion and a combination dose escalation. The monotherapy portion of the study includes R/R MDS patients with and without a spliceosome mutation and R/R AML patients with and without a FLT3 mutation. The combination therapy portion of the study includes two arms: CA-4948 plus azacitidine, for patients naïve to HMA, and CA-4948 plus venetoclax, for patients naïve to venetoclax.
When combined with azacitidine, CA-4948 will be dosed at 200 mg twice daily for 21 days of a 28-day cycle, followed by a 300 mg dose cohort if tolerability allows. Azacitidine will be given in 7 consecutive doses or split doses starting at 75 mg/m2.
When combined with venetoclax, CA-4948 will be dosed at 200 mg twice daily for 21 days of a 28-day cycle, followed by a 300 mg cohort if tolerability allows. Venetoclax will be administered at 100 mg orally with a ramp up over 3 days to 400 mg for 21 days of a 28-day cycle.
The primary objective of the combination portion of the study is to determine the recommended Phase 2 dose (RP2D) for CA-4948 in combination with azacitidine and in combination with venetoclax based on safety and tolerability, dose-limiting toxicities (DLT), and any biologic activity, pharmacokinetic and pharmacodynamic findings from the study population. Additional objectives include characterization of CA-4948’s pharmacokinetic parameters and overall response rate.