Sunesis announces preliminary data from Phase 1b/2 trial of Vecabrutinib
Sunesis Pharmaceuticals announced the presentation of results 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. Preliminary data reported were available from 23 patients treated in the trial thus far. These included 19 CLL patients, two mantle cell lymphoma patients, and two Waldenstrom Macroglobulinemia patients. Patients had received an average of 4 lines of prior therapy, and all patients had progressed on prior BTKi therapy. 61% of CLL patients enrolled had a BTK C481 mutation as of the data cutoff for the poster. Preliminary data on treatment-emergent adverse events were available for 20 patients. The most common TEAEs of any grade were anemia and neutropenia and night sweats, with 5 drug-related Grade 3 adverse events occurring in 3 patients, all in cohort 2. In total, there were 8 serious adverse events in six patients, none of which were considered drug-related. Stable disease was seen in 4 CLL patients, 3 of whom had BTK C481S mutations. Two of these patients, both with BTK C481S mutations, showed decreases of 16% and 47% in index lesions at first assessment by CT scans. The patient with the 47% decrease was one of two evaluable post-venetoclax patients with the BTK C481S mutation. A patient with WM experienced clinical benefit with improvement in B-symptoms but no impact on immunoglobulin M. One patient in cohort 3 continues on treatment in cycle 6. The pharmacokinetic profile of vecabrutinib showed sustained exposure over the dosing interval, with median steady-state trough concentrations increasing with dose. Preliminary data showed near doubling of trough concentrations between doses of 50 mg and 100 mg. Based on the results of the Phase 1A study in healthy subjects, trough levels of greater than1,000 ng/mL are expected to be required for consistent BTK inhibition and greater clinical activity. This is likely achievable with doses higher than 100 mg BID. Vecabrutinib inhibition of BTK phosphorylation was rapid and sustained in patients who had adequate baseline signal for analysis. Decreases in serum concentrations of key cytokines associated with B-cell malignancies, CCL2, CCL3, and CCL4, were observed in most evaluable patients, consistent with inhibition of BTK signaling.