ArQule, Inc. announced final results from the phase 1 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 American Society of Hematology (ASH) 2019 Annual Meeting & Exposition in Orlando, Florida. Key Findings: 65 mg QD was selected as the Recommended Phase 2 Dose (RP2D) for further studies; Across all disease subsets, ARQ 531 showed a low incidence of associated toxicities, including one grade three DLT and no atrial fibrillation or bleeding observed; At 65 mg QD, ARQ 531 has a steady state mean Cmin above 1 µM and long plasma half-life of 56 hours resulting in complete pBTK inhibition. Clinical Anti-Tumor Activity: In CLL, an Overall Response Rate (ORR) of 89% (8/9 responses in evaluable patients) was achieved in heavily pretreated R/R CLL patients (7/8 harboring BTK-C481S mutation) dosed at =65 mg QD. Eleven of 19 patients treated at 65 mg QD remain on study; In Richter’s Transformation, an ORR of 50% (3/6 responses in evaluable patients) was achieved at 65 mg QD Two additional PRs were observed including one patient with Follicular Lymphoma (FL) and 1 patient with Diffuse Large B-cell Lymphoma (DLBCL). Durability: 00% (5/5) evaluable CLL patients that received a third scan (cycle 9) are durable confirmed PRs and remain on therapy; 67% (2/3) of Richter’s patients that achieved PRs came off study after becoming eligible for CAR-T therapy; The Follicular Lymphoma patient that achieved a PR has been on study for 120 weeks and remains a PR and on therapy. The reported data are from the phase 1, open label, single arm dose escalation study and include patients (n=47) initially dosed at levels of 5, 10, 15, 20, 30, 45, 65 and 75 mg once a day with relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), Richter’s Transformation, Waldenström macroglobulinemia and other B-cell Non-Hodgkin lymphomas.