Biotechnology company Curis has dosed the first patient in its Phase 1 trial of CA-4948 and ibrutinib combination in patients with relapsed or refractory (R/R) hematologic malignancies.
CA-4948 is a novel, small molecule IRAK4 kinase inhibitor, while ibrutinib is a BTK inhibitor.
The two-part, multi-centre, open-label, dose-escalation and expansion study will assess the safety, pharmacokinetics, pharmacodynamics, clinical activity and biomarker correlations of CA-4948 and ibrutinib in the patients.
Part 1 is a dose-escalation using a 3+3 design and will enrol 18 patients. They will be given a starting dose of 200mg CA-4948 BID with subsequent escalation to 300mg BID, plus ibrutinib doses appropriate for their respective NHL subtype.
Safety and tolerability, maximum tolerated dose and the recommended Phase II dose will be the primary endpoints of Part 1 of the study, while secondary objectives will be pharmacokinetics and preliminary efficacy.
Biomarker correlations such as MYD88-L265P mutations and IRAK4 pathway and NFκB inhibition will form exploratory objectives.
Part 2 will enrol subjects into four cohorts: marginal zone lymphoma (MZL), ABC-DLBCL, primary central nervous system lymphoma (PCNSL) and NHL with adaptive ibrutinib resistance.
Curis will carry out an interim futility analysis on enrolling 15-20 patients in each cohort.
Complete response or objective response rate and duration of response compared to historical controls will form the primary endpoints of Part 2.
Curis president and CEO James Dentzer said: “In dosing the first patient in this Phase I study evaluating CA-4948 and ibrutinib, we are taking a highly anticipated step forward in bringing a potent oral therapeutic regimen to patients with relapsed or refractory hematologic malignancies.
“BTK inhibitors are an approved category of therapies for patients with various lymphatic cancers yet they only target one of the two main pathways activating NF-κB in B-cell malignancies.”
In 2018, Curis started dosing patients in a Phase l trial of CA-4948 to treat patients with lymphoma.