Interim results from a phase I study of CAL-101, a selective oral inhibitor of phosphatidylinositol 3-kinase p110d isoform, in patients with relapsed or refractory hematologic malignancies.

Abstract

3032 Background: The class I phosphatidylinositol 3-kinase (PI3K) p110δ isoform is primarily expressed in cells of hematopoietic origin and has a key role in B cell maturation and function. CAL-101 is a potent and selective inhibitor of p110δ that inhibits PI3K signaling and induces apoptosis of primary CLL and AML cells and a range of leukemia and lymphoma cell lines. Methods: An ongoing phase 1 study enrolled previously treated patients with select hematologic malignancies in a standard sequential dose escalation/cohort expansion design. CAL-101 was administered orally twice-a-day continuously for 28 days per cycle. Results: At data cutoff, 57 patients were enrolled (NHL n=29, CLL n=18, AML n=10), 49% had refractory disease, median number of prior regimens= 4.5. Dose levels were 50 mg (n=3), 100 mg (n=3), 200 mg (n=34) and 350 mg (n=17). Clinical responses were seen at all dose levels. The objective response rate was 9/15 in indolent NHL, 6/7 in mantle cell lymphoma, and 4/17 in CLL, with 14/16 evaluabl...