Background: CD47, a marker of self, is a myeloid checkpoint that is upregulated by tumor cells to evade the host’s immune response. ALX148 is a fusion protein comprised of an engineered high affinity CD47 binding domain of SIRPα genetically linked to an inactive Fc region of human immunoglobulin. We have previously shown ALX148 blocks CD47 and safely enhances the activity of targeted anticancer antibodies and checkpoint inhibitors through Fc dependent and independent mechanisms in nonclinical models (ASH 2017 #112). Methods: As of Feb 07, 2018, 30 patients (pts) were enrolled to escalating dose cohorts of ALX148 (0.3 mg/kg [mpk] IV every week [QW] - 30 mpk every other week [QoW]) as a single agent (Part 1) or in combination with standard regimens of pembrolizumab (P), trastuzumab (T), or rituximab (R) (Part2). The primary endpoint for each Part is first cycle dose limiting toxicity (DLT). Tumor response, pharmacokinetics (PK), and CD47 target occupancy (TO) are also characterized. Results: Part 1 results are summarized. 25 pts received single agent ALX148. 22 pts experienced any AE. Maximum CTCAE treatment related AEs that occurred in > 1 pt were Dizziness 2G1; Fatigue 3G1; Headache 4G1; Rash 1G1,1G2; and Thrombocytopenia 2G3. Two pts experienced a DLT (Neutropenia with infection, 3mpk; Thrombocytopenia with significant bleed, 30 mpk). There were 4 pts who reported ≥G3 AE (Infection 1G3, 3mpk; Pancreatitis 1G3, 30 mpk; Thrombocytopenia 1G3, 3 mpk and 1G3, 30 mpk; Neutropenia 1G4, 3mpk) and 1G5 Death (30mpk; etiology being investigated). No single agent MTD was identified, and the maximum administered dose (MAD) was 30 mpk QoW. Four pts achieved stable disease including 1 pt with NSCLC who had a 15% tumor reduction. ALX148 demonstrated linear PK at doses ≥ 10 mpk QW and full TO at doses ≥ 3 mpk QW. To date, 5 Part 2 pts received ALX148 (10 mpk QW) in combination (3 with P; 1 with T; 1 with R). Conclusions: ALX148 is generally well tolerated in pts with advanced tumors with favorable PK/TO characteristics at doses evaluated. The MAD of single agent ALX148 is 30 mpk QoW. Accrual to the Part 2 combination cohorts is ongoing. Clinical trial information: NCT03013218