Background: ASN002 is a novel, potent inhibitor of Janus Kinases (JAK) and Spleen Tyrosine Kinase (SYK). 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 evaluated escalating ASN002 oral doses of 10, 20, 30, 40, 50 and 75 mg BID and 80 and 120 mg QD. Phase 1 allowed patients with solid tumors or hematologic malignancies; Phase 2 allows only patients with mantle cell lymphoma (MCL), myelofibrosis (MF), Peripheral T-cell Lymphoma (PTCL) and Chronic Lymphocytic Leukemia (CLL). Endpoints include safety, tolerability, pharmacokinetics, serum markers of inflammation, and response using Lugano criteria (NHL), IWG-MRT (MF), or IWG-CLL. Results: Forty-six patients have enrolled in the study at doses of 10 –75 mg BID and 80-120 mg QD. All patients had multiple prior lines of treatment (range: 2 – 8). ASN002 was well tolerated at doses up to 75 mg BID. The DLT at 100 mg BID was Grade 3 infection. 75 mg BID was the recommended Phase 2 dose. 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 increased in a dose related manner up to 100 mg BID. Robust reduction of inflammatory markers CRP, IL-18, MIP1β, VCAM-1, TNFR2 was observed at all dose levels. Stable disease (9+ months) in a patient with primary peritoneal cancer, about 50% reduction in target lesions at 3 months in a FL patient, stable disease and reduction of pruritus in a PTCL patient after 2 months, and significant disappearance of skin lesions in another PTCL patient after one month were observed. Early improvement in symptoms within 2 weeks of treatment in MF has also been reported in an ongoing patient. Accrual of patients continues. Conclusions: ASN002 was safe and well tolerated. Encouraging preliminary evidence of efficacy in NHL and MF patients was observed. Updated and detailed results will be presented. Clinical trial information: NCT02440685