On June 14, 2019 ArQule, Inc. (Nasdaq: ARQL) reported preliminary results from the Company’s phase 1 dose escalation study for ARQ 531, an orally bioavailable, potent and reversible dual inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) in patients with relapsed or refractory hematologic malignancies at the 2019 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting in Amsterdam, the Netherlands (Press release, ArQule, JUN 14, 2019, View Source [SID1234537072]).
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"The profile of ARQ 531 continues to strengthen, and we are delighted to be able to demonstrate such compelling clinical activity at a well-tolerated dose in patients who have already exhausted available therapies," commented Dr. Brian Schwartz, Chief Medical Officer of ArQule. "We are now focused on finalizing the recommended phase 2 dose and planning for the expansion of our clinical efforts with ARQ 531 into later stage trials across multiple indications as a single agent and as a combination therapy."
"ARQ 531 was selected and extensively tested preclinically to address the emerging therapeutic need for patients who have become resistant to covalent BTK inhibitors," commented Dr. Jennifer Woyach, Associate Professor of Medicine at The Ohio State University and the Principal Investigator of the study. "The data presented in this poster provide compelling clinical proof-of-concept for this novel class of reversible BTK inhibitors and was predicted by the preclinical studies published in Cancer Discovery1 last year."
The reported data are from the ongoing phase 1, open label, single arm dose escalation study and include the first eight cohorts (n=34) at dose levels of 5, 10, 15, 20, 30, 45, 65 and 75 mg once a day in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Richter’s Transformation, Waldenström macroglobulinemia and other B-cell Non-Hodgkin lymphomas. Cohort 8 (75 mg) enrollment is ongoing.
Key findings presented include the following:
ARQ 531 is well-tolerated through 65 mg QD
Pharmacokinetic data demonstrate a steady-state mean Cmin of above 1 µM in patients receiving ≥45 mg QD. The plasma half-life ranges from 20-30 hours
Pharmacodynamic data at doses above 20-30 mg QD is associated with complete pBTK inhibition and substantial CCL3 suppression
Robust, dose-dependent, anti-tumor activity was observed
ORR of 66% (4 responses in 6 evaluable patients) was observed in heavily pretreated R/R CLL patients, all with the BTK-C481S mutation, from cohort 7
A partial response was observed in the first patient with Richter’s Transformation, who had progressed on ibrutinib and R-CHOP, suggesting that ARQ 531’s distinct MOA is amenable to target this highly unmet medical need
A Follicular Lymphoma patient remains a confirmed PR and has been on therapy approximately two years, providing valuable initial insights into long- term safety as well as durability of response
The poster at EHA (Free EHA Whitepaper) presenting these data entitled, "A Phase 1 Dose Escalation Study of ARQ 531 in Patients with Relapsed or Refractory B-Cell Lymphoid Malignancies," is available on the company’s website at www.arqule.com/publications-presentations/.
ArQule will host a conference call and webcast for investors on Friday, June 14, 2019 at 8:00 a.m. EDT to discuss the ARQ 531 clinical data. The live webcast can be accessed in the "Investors and Media" section of our website, www.arqule.com, under "Events & Presentations" or by clicking here. You may also listen to the call by dialing 1-800-239-9838 within the U.S. or 1-323-794-2551 outside the U.S. and providing conference ID 3110780. A replay will be available two hours after the completion of the call and can be accessed in the "Investors & Media" section of our website, www.arqule.com, under "Events and Presentations."
About BTK and ARQ 531
Bruton’s tyrosine kinase, BTK, is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers. ARQ 531 is an orally bioavailable, potent and reversible dual inhibitor of both wild type and C481S-mutant BTK. The C481S-mutation is a known resistance mechanism for first generation irreversible BTK inhibitors. ARQ 531 has demonstrated a good safety profile, predictable PK, profound pharmacodynamic effects and emerging signs of dose-proportional clinical activity in phase 1 clinical testing.