Calistoga Pharmaceuticals, Inc., the leader in the development of isoform-selective phosphatidylinositol 3 kinase (PI3K) inhibitors for the treatment of cancer and inflammatory diseases, today presented preclinical and clinical data on CAL-101, the Company's oral, delta selective PI3K inhibitor at the 15th Congress of the European Hematology Association in Barcelona, Spain. Results from the interim assessment of the ongoing Phase 1 clinical trial demonstrate clinical benefit in patients with relapsed or refractory indolent non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL). Preclinical results assessing selected chemokines in plasma and circulating CLL cells from patients in the Phase 1 clinical trial support that CAL-101 inhibits chemokine signaling and production from CLL cells and the microenvironment. These results elucidate the novel biological effects of CAL-101 and are consistent with the single agent activity observed in Phase 1 evaluation, particularly the biologic activity observed in nearly all CLL patients.
“We continue to be encouraged with the clinical benefit we are observing with this novel mechanism and look forward to participating in future trials with CAL-101”
The clinical results presented were from an interim assessment of patients enrolled in the ongoing Phase 1 study of CAL-101 in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), indolent and aggressive non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML) and multiple myeloma (MM). Over half of the patients enrolled in the trial were refractory to their last therapy prior to entering the study, and the median number of prior treatment regimens was five. Patients received continuous, twice daily, oral dosing of CAL-101 on a 28-day cycle for up to 12 cycles.
Single agent CAL-101 treatment in patients with relapsed or refractory indolent non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL), resulted in overall response rates of 57 percent, 67 percent, and 30 percent, respectively.
Overall, CAL-101 was generally well tolerated. A low incidence of hematological toxicity was observed. Some patients had elevation of liver transaminases, which was monitorable and reversible following discontinuation of dosing. Most patients who experienced an elevation in transaminases resumed CAL-101 at a reduced dose.
In the CLL patients, eighty-four percent of patients had bulky disease defined as lymph nodes greater than five centimeters in size; bulky disease is typically more difficult to treat. In 29 of 31, or 94 percent, of CLL patients, treatment with CAL-101 resulted in a greater than 50 percent decrease in their lymph node disease. In addition, 14 of 20, or 70 percent, of CLL patients with low platelet counts entering the study had meaningful improvements, which provides another indication of clinical benefit.