On December 7, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported updated data from its ongoing Phase 1, open-label, 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, and also declared the recommended Phase 2 dose of the investigational drug (Press release, Curis, DEC 7, 2020, View Source [SID1234572336]). The new results, which will be shared in a virtual oral presentation at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, show that the recommended Phase 2 dose of 300 mg BID of CA-4948 monotherapy provides potent and durable anti-cancer activity in patients with relapsed or refractory non-Hodgkin’s lymphoma.

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"We are tremendously pleased to report that IRAK4 inhibition with CA-4948 monotherapy could potentially offer a novel treatment approach for patients with NHL," said James Dentzer, President and Chief Executive Officer of Curis. "We believe these preliminary data, demonstrating the tolerability and durable anti-cancer activity of single-agent CA-4948 therapy for these extremely sick patients, validate our development approach for this program and reaffirm our enthusiasm for the therapeutic potential of a combination therapy with proven synergistic treatments like ibrutinib. Anti-cancer activity was observed across multiple dose levels, which provides additional flexibility as we continue to develop CA-4948 for NHL. Among the active dose levels, we believe that 300 mg twice-daily has the potential to strike the most favorable balance of durable anti-cancer activity and tolerability for long-term treatment. We are also highly encouraged by the data gathered on our two exploratory biomarkers, which we believe support a compelling patient enrichment strategy. We are eager to work with our investigators, clinicians, and the broader patient community to advance the development of this novel treatment approach in a patient population in need of better treatment options."

"CA-4948 consistently reduced tumor burden at the recommended Phase 2 dose of 300 mg twice daily. Data like these, even at this early stage, are compelling for the patients and physicians contending with this degree of relapsed or refractory disease," said Robert Martell, Head of R&D of Curis. "These are patients facing the poorest prognoses after numerous prior lines of other therapies failed to meaningfully temper their disease progression. For these patients, any degree of tumor reduction may represent a significant improvement. Equally promising is the prospect of long-term tumor reduction and tolerability. This profile, along with the unique synergistic potential of a CA-4948/BTK inhibitor combination, could potentially offer a groundbreaking development in a disease area with considerable need."

The reported updated preliminary 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, anti-cancer activity, and biomarker correlations, in patients with R/R NHL. Seven dosing cohorts have been treated in continuous 21-day cycles at levels of 50 mg and 100 mg once-daily (QD), and 50 mg, 100 mg, 200 mg, 300 mg, or 400 mg twice-daily (BID). The data being reported from this ongoing trial are preliminary and subject to change.

Key findings from the ongoing Phase 1 study include:

CA-4948 was demonstrated to be generally well-tolerated, most AEs have been Grade 1-2.
Preliminary tolerability profile supports potential long-term treatment and combination with other active drugs against NHL.
Enrolled patients include those with DLBCL, WM, marginal zone lymphoma (MZL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), transformed high-grade-B-Cell lymphoma (HGBCL), and mantle cell lymphoma (MCL).
Patients enrolled experienced a median of 4 prior lines of treatment (range 1-8).
Anti-cancer activity, as measured by reduction of tumor burden, was observed in:
6 of 7 evaluable patients receiving RP2D of 300 mg BID, with a mean reduction of 27% (ranging from 6% to 67%).
One patient with WM, who dose escalated from 50mg to 100mg to 200mg to 300mg (all doses, BID), experienced dose-dependent reductions in tumor burden at each dose level, eventually reaching a tumor burden reduction of 67% (partial response) following escalation to the 300mg BID dose. This patient continues to remain on therapy after 728 days (as of December 7th, 2020).
3 patients have been on therapy for greater than 1 year.
Encouraging early data for two potential biomarkers (NF-κB p-p50 and MYD88).
Early data for NF-κB p-p50 biomarker may support patient selection:
Patients whose tumors do not exhibit NF-κB activity may not be amenable to NF-κB downregulation.
7 of 7 patients testing negative for p-p50 at baseline experienced disease progression.
2 of these patients were dosed at 200mg BID.
Patients whose tumors do exhibit NF-κB activity may be amenable to NF-κB downregulation.
6 of 7 patients testing positive for p-p50 at baseline achieved stable disease or tumor shrinkage.
1 of these patients was dosed at 300mg BID.
Early data for MYD88 biomarker may support patient enrichment:
Both patients identified as positive for MYD88 mutation experienced tumor reduction, including a partial response.
More data are needed to confirm this potential predictive biomarker, but we believe positive patient outcomes are consistent with the thesis that patients with MYD88-mutated tumors should benefit from IRAK4 inhibition.
Webcast Event Information

Curis management will host a virtual KOL event tomorrow, December 8, 2020 at 8:00 am ET to discuss these results with Dr. Amit Verma, Professor of Medicine-Oncology at Albert Einstein College of Medicine, and Director of the MDS Program at Montefiore Medical Center located in Bronx, NY. To access the webcast, please visit the Events and Presentations section of the Curis website at View Source