Background: ASN002 is a novel, potent inhibitor of Spleen Tyrosine Kinase (SYK) and Janus Kinases (JAK). Pre-clinical studies indicate that ASN002 has low nM IC50s against SYK and JAK, decreases proliferation in ibrutinib-resistant cell lines, and suppresses tumor growth in rodent xenograft models of NHL and other hematologic malignancies. Methods: This Phase 1/2 clinical trial in patients with solid tumors and hematologic malignancies evaluates escalating ASN002 oral doses of 10, 20, 30, 40, 50 and’ 75 mg BID and 80 and 120 mg QD mg (NCT02440685). Phase 1 allows patients with solid tumors or hematologic malignancies; Phase 2 allows only patients with diffuse large B-Cell lymphoma (DLBCL), follicular lymphoma (FL) or mantle cell lymphoma (MCL). Endpoints include safety, tolerability, pharmacokinetics, serum markers of inflammation, and response using RECIST or Lugano Classification System. Results: Twenty-eight patients have enrolled in the DLT phase at doses of 10 mg – 75 mg BID and at 80 mg QD. All patients had multiple prior lines of treatment (range: 2 – 8). ASN002 was well tolerated. No dose limiting adverse events have been reported at these dose levels. Most drug-related adverse events were Gr 1/2 (e.g. headache, fatigue). Steady-state systemic exposure was high (C_max, AUC (0-12h) and T_1/2 at 40 mg BID were 0.7 µM, 6.3 µM.h and 18 h, respectively). High systemic exposure was also observed at 80 mg QD. Robust reduction of CRP, IL-18, MIP1β, VCAM-1, TNFR2 was observed at all doses. Stable disease (RECIST, 9+ months) in a patient with primary peritoneal cancer, about 50% reduction in target lesions at 3 months in a FL patient (Lugano, 6 prior lines) and stable disease and reduction of pruritus in a peripheral T-Cell lymphoma patient after 2 months (Lugano, 2 prior lines) of treatment were observed. ASN002 treatment continues in both lymphoma patients. Accrual of patients continues. Conclusions: ASN002 was safe and well tolerated. Encouraging preliminary evidence of efficacy in NHL patients was observed. MTD has not been reached and dose escalation continues. Updated and detailed results will be presented. Clinical trial information: NCT02440685