Curis (CRIS) a company that engages in the development and commercialization of drug candidates for the treatment of human cancers (CUDC-907, CA-4948, CA-170 and CA-327) today announced positive preliminary data from its ongoing open-label, single arm Phase 1 dose escalation study of CA-4948, a novel, small molecule IRAK4 kinase inhibitor, in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS).
IRAK4 plays an essential role in the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways, and these pathways are frequently dysregulated in patients with AML and MDS. 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. A variety of drivers are believed to cause this, including specific spliceosome mutations.
“We are highly encouraged by the breadth of clinical activity with CA-4948 seen with this early data, especially as this study is both monotherapy and in a late line, relapsed/refractory population. Historically, monotherapy studies in AML and MDS have proven underwhelming; monotherapy studies in a relapsed/refractory setting have been especially challenging, we also have been pleased by the pace at which our trial partners have been able to enroll patients. We look forward to continuing to advance CA-4948 and reporting additional Phase 1 data in the second half of 2021.”James Dentzer, President and Chief Executive Officer of Curis.
The reported preliminary data are from Curis’s ongoing open-label, single arm Phase 1 dose escalation 3+3 study of orally administered CA-4948 monotherapy in adult patients with AML or high-risk MDS.
A minimum of 3 patients will be enrolled in each cohort of the two-part study, starting with 200 mg BID, which was demonstrated to be well-tolerated, capable of achieving relevant levels of drug exposure and has demonstrated signs of biologic activity in Curis’s ongoing Phase 1 study of CA-4948 for the treatment of patients with relapsed or refractory non-Hodgkin’s lymphoma.
The primary objective of the study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for CA-4948 based on safety and tolerability, dose-limiting toxicities (DLT), and any biologic activity, pharmacokinetic and pharmacodynamic findings from the study trial population.
Additional objectives include characterization of CA-4948’s pharmacokinetic parameters, and biomarker correlations. As of November 23, 2020, 4 AML patients and 3 high-risk MDS patients had been enrolled in the first 2 study cohorts and no DLTs had been observed. The data being reported from this ongoing trial are preliminary and subject to change.
Key findings include:
- Marrow blast reductions observed in all evaluable patients (6 patients).
- 6 of 7 patients enrolled remain on study.
- Patients enrolled experienced a median of 3 prior lines of treatment (range 1-4).
- Two patients experienced a marrow complete response, one with blast count going from 23% pretreatment to 1% on treatment, and the other going from 11% pretreatment to 2% on treatment.
- No DLTs observed in 7 DLT-evaluable patients in the 200 mg BID and 300 mg BID cohorts.
- Enrollment has begun in the 400 mg BID cohort.