Sunesis Pharmaceuticals announced data from the Company's Phase 1b/2 clinical trial of its non-covalent BTK inhibitor vecabrutinib in adults with relapsed/refractory chronic lymphocytic leukemia and other B-cell malignancies. The results will be presented on Sunday, December 8, from 6:00-8:00 p.m. ET in a poster session titled "CLL: Therapy, excluding Transplantation: Poster II" at the 60th American Society of Hematology Annual Meeting in Orlando, Florida. The poster, titled "Ongoing Results of a Phase 1b/2 Dose Escalation and Cohort-Expansion Study of the Selective, Noncovalent, Reversible Bruton's Tyrosine Kinase Inhibitor, Vecabrutinib, in B-Cell Malignancies," Abstract No. 3041, will be available at www.sunesis.com on Sunday. The data are being disclosed in advance of the ASH meeting due to an unauthorized disclosure of the poster on social media this morning. Data reported today were from 29 relapsed/refractory patients treated in Cohorts 1 to 5. These included 23 patients with CLL, three with Waldenstrom macroglobulinemia, two with mantle cell lymphoma and one with marginal zone lymphoma. Patients had received an average of 4 lines of prior therapy, and all had progressed on prior BTK inhibitor therapy; 61% of the CLL patients had a BTK C481 mutation. The poster builds vecabrutinib's profile in four key areas: Safety: The most common treatment-emergent adverse events of any grade were anemia, headache, and night sweats. Headache and nausea were the two most common drug-related TEAEs. To date, no drug-related Grade 3 or Grade 4 TEAEs have been observed at dose levels higher than 50 mg. Activity: Clinical benefit has been observed in covalent BTK inhibitor-resistant patients with poor prognostic features and in both wild-type and C481-mutated BTK disease. In the 300mg dose group, stable disease was observed in 3 of 5 patients, and two remain on treatment in Cycle 5 and Cycle 6, including a wild-type BTK CLL patient with -40% change in tumor burden at first scan. In addition, one patient from Cohort 3 remains on study in Cycle 12, having been dose escalated twice from their initial dose of 100 mg to their current dose of 300 mg. Pharmacokinetics: Vecabrutinib showed sustained exposure over the dosing interval with both exposure and median steady-state minimum blood plasma concentration increasing with dose. On Day 8, steady-state median Cmin values were 75 ng/mL, 451 ng/mL, 873 ng/mL, 1124 ng/mL, and 1950 ng/mL. Pharmacodynamics: Vecabrutinib's pharmacodynamic effects increased with dose in CLL patients and indicate increased impact on BTK signaling as dose is escalated.
