On December 6, 2019 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported updated preliminary data from its ongoing Phase 1 dose escalation study of CA-4948, an IRAK4 kinase inhibitor, for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin’s lymphoma (NHL), including patients with diffuse large B-cell lymphoma (DLBCL), Waldenström’s macroglobulinemia (WM) and oncogenic MYD88 mutations (Press release, Curis, DEC 6, 2019, View Source [SID1234551999]).

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"We are very encouraged by the anti-cancer activity that we have observed to date from CA-4948 during dose escalation in our Phase 1 study," said Robert Martell, MD, PhD, Head of R&D at Curis. "Notably, five of the six patients evaluable for anti-cancer activity at the two highest dose levels of CA-4948 have experienced reduced tumor burden. Additionally, treatment for three of these five patients is ongoing after 33 to 51 weeks. These findings illustrate dose dependent activity compared to earlier dose levels."

Dr. Martell continued: "We believe these results achieve the desired activity outcome for a targeted single agent treating malignancies with complex molecular genetics. Unlike the minority of cancers with a single driver mutation, these genetically complex malignancies have aberrant signaling through multiple signaling pathways. One such pathway is the oncogenic TLR pathway, which depends on IRAK4. Such complex cancers represent the bulk of actual medical need in oncology today, and we believe the most effective therapeutic approaches in these situations is to target multiple such mechanisms. Indeed, synergy was observed preclinically when combining CA-4948 with either BTK inhibitors or a BCL2 inhibitor, and we intend to explore combinations in the clinic."

"We believe these updated clinical data further support the potential of CA-4948 to become a safe, effective therapeutic option for patients with NHL," said James Dentzer, President and Chief Executive Officer of Curis. "CA-4948 is currently the most advanced molecule targeting IRAK4 in clinical development for cancer and given these exciting results, we intend to move aggressively to advance CA-4948 with the goal of bringing this promising new therapy to patients in need. We look forward to expanding the development of CA-4948 with two new clinical trials in 2020 that will study CA-4948 in AML/MDS and in combination therapy in NHL."

The reported data are from Curis’s ongoing Phase 1, open-label, dose escalation 3+3 study designed to evaluate the safety and tolerability of CA-4948, in addition to pharmacokinetics, pharmacodynamics, and anti-cancer activity, in patients with R/R NHL. Patients have been treated in continuous 21-day cycles and at dose levels of 50mg once-daily (QD), 50mg twice-daily (BID), 100mg QD, 100mg BID, 200mg BID and 400mg BID.

Key findings include:

CA-4948 was demonstrated to be generally well-tolerated.
Patients enrolled to date include patients with tumor types of DLBCL, WM, marginal zone lymphoma, follicular lymphoma, and lymphoplasmacytic lymphoma.
Anti-cancer activity, as measured by the reduction of tumor burden, was observed in:
5 out of 6 evaluable patients in the highest dose cohorts of 200mg BID and 400mg BID, with a mean reduction of 29% (ranging from 5% to 47%).
One patient with WM, who dose escalated from 50mg BID to 100mg BID, and then to 200mg BID, experienced dose-corresponding reductions in tumor burden. This patient remains on therapy.
One patient with DLBCL enrolled in the 200mg dose cohort remains on study and has seen tumor reductions of 35%.
One patient treated at 100mg QD had a dose-limiting toxicity (DLT) of maculo-papular rash, which was resolved after steroid treatment. Another patient treated at 400mg BID experienced a DLT of Grade 3 rhabdomyolysis.
Curis is currently evaluating patients at the 400mg BID dose of CA-4948 in its Phase 1 study and plans to continue dose escalation until the maximum tolerated dose and or recommended Phase 2 dose of CA-4948 is determined.

Conference Call Information

Curis management will host a conference call today, December 6, 2019, at 8:00 a.m. ET, to discuss these results. To access the live conference call, please dial 1-888-346-6389 from the United States or 1-412-317-5252 from other locations, shortly before 8:00 a.m. ET. The conference call can also be accessed on the Curis website at www.curis.com in the Investors section.