501 Immunological STAT3 knockdown associated with anti-tumor activity in pre-clinical models translates to clinical samples, suggesting immune modulation contributes to the clinical activity of AZD9150, a therapeutic STAT3 ASO

in relapsed/refractory non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) have been reported (Dreyling et al, ASH 2013). We report here updated primary efficacy results per independent radiologic reviews. Methods: Patients with histologically confirmed indolent or aggressive lymphoma or CLL, relapsed or refractory to 2 prior lines of treatment were enrolled. Copanlisib (0.8 mg/kg, iv) was administered on days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: A total of 33 patients with indolent NHL (iNHL) or CLL and 34 with aggressive NHL were treated (Table); median age 68 years; M/F = 32/35; median number of previous lines of treatment = 3; previous exposure to rituximab = 59. At the time of this analysis, 14 patients remain on treatment; median cycles administered = 4. In the indolent group, the ORR was 47% (90% CI 32−63) overall and 53% [90% CI, 32−73] in iNHL. In the aggressive NHL group, the ORR was 29% (90% CI, 17−45). Complete responses (CR) were observed in FL, MCL, and PTCL (Table). The most common adverse events (AEs) of all grades (G) were hyperglycemia (63%), hypertension (61%), fatigue (45%) and diarrhea (40%). G3−4 AEs occurring in >10% of patients included: hypertension (43%), neutropenia (27%), hyperglycemia (25%), and anemia (13%). AEs leading to dose modifications or permanent discontinuation occurred in 55% and 25% of patients, respectively. There were 3 drug-related grade 5 events: lung infection, meningitis and respiratory failure. Summary/Conclusions: Copanlisib is active as a single agent in heavily pretreated patients with relapsed/refractory indolent or aggressive lymphoma, with CRs demonstrated in FL, MCL, and PTCL. An acceptable toxicity profile was observed. Additional studies in patients with iNHL and selective aggressive lymphoma are ongoing.