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 announced
updated clinical data on CAL-101, the Company’s oral, delta selective
PI3K inhibitor, presented during two oral presentations at the 51st
American Society of Hematology Annual Meeting in New Orleans. Interim
data from an ongoing Phase 1 study evaluating CAL-101 in patients with
hematologic malignancies demonstrated impressive single agent
activity. In patients with relapsed or refractory indolent non-Hodgkin’s
lymphoma (NHL), mantle cell lymphoma, and chronic lymphocytic leukemia
(CLL), overall responses rates of 60 percent, 86 percent, and 24 percent
were observed, respectively. Preclinical data demonstrated that the
delta isoform of PI3K is overexpressed and frequently activated in B
cell malignancies. Treatment with CAL-101 induced cell death and also
inhibited signaling pathways associated with cancer cell dependence on
the tumor microenvironment.
Results were presented from the ongoing Phase 1 study of CAL-101, which
is enrolling patients with relapsed or refractory CLL, indolent and
aggressive B-cell NHL, or acute myeloid leukemia. The data are an
interim evaluation of 57 patients. Of the 15 evaluable indolent NHL
patients, partial responses, defined as a decrease in tumor burden of
greater than 50 percent, were observed in nine patients. In the cohort
of aggressive NHL patients, partial responses were observed in six of
seven mantle cell lymphoma patients. Partial responses were observed in
four of 17 CLL patients; however, 14 of 16 (88 percent) CLL patients’
enlarged lymph nodes decreased in size by more than 50 percent.
Approximately 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 4.5. The duration of response with
CAL-101 is not yet established, however the longest duration of response
seen to date is 9 months in a patient with follicular lymphoma, which is
longer than the response to any of the 6 prior regimens this patient
received, including autologous hematopoietic stem cell transplant.
Overall, CAL-101 was generally well tolerated. A low incidence of
hematological toxicity was observed. As frequently occurs in this
patient population, the most common serious adverse event was infection.
The dose limiting toxicity in the study was elevation of liver
transaminases, which was monitorable and reversible following
discontinuation of dosing. Most patients resumed CAL-101 at a reduced
dose.
“These results with CAL-101 are very encouraging, with clinical
responses attained in previously treated NHL and CLL patients, and
provides validation for the importance of the PI3K delta pathway,” said
Ian W. Flinn, M.D., Ph.D., Director of Hematologic
Malignancies Research at the Sarah Cannon Research Institute who
presented the clinical results at ASH.