Analysis Of Ox40 Agonist Antibody (Pf-04518600) In Patients With Hepatocellular Carcinoma

523 Background: PF-04518600 (PF-8600) is a humanized agonist IgG2 monoclonal antibody to the tumor necrosis factor superfamily receptor OX40. PF-8600 was given to patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC) in dose expansion of a phase 1 study (NCT02315066). Safety and tolerability were primary endpoints and exploratory endpoints included biomarker analyses. Methods: Pts received either 30 mg (Arm 1) or 250 mg (Arm 2) of PF-8600 intravenously Q2W. Pts had pathologic diagnosis of advanced HCC, a Child-Pugh score of A or B7, and had ≤2 prior lines of therapy, or if treatment naïve, had declined standard of care. Radiological tumor assessments were conducted Q8W. Biopsy samples collected at baseline and wk 6 were analyzed by immunohistochemistry and RNA sequencing for pharmacodynamic (PD) analyses. Whole blood samples were collected longitudinally for DNA extraction for high-throughput sequencing of the T cell receptor β-chain. Results: Arm 1 enrolled 16 pts (mean age 65.6 yrs; range 54-81 yrs; prior PD-1/PD-L1: 5 pts) and Arm 2 enrolled 19 pts (mean age 61.7 yrs; range 26-79 yrs; prior PD-1/PD-L1: 3 pts). All grade treatment related adverse events (TRAEs) occurred in 69% of pts in Arm 1 and 58% of pts in Arm 2. The rate of ≥Grade 3 TRAEs was 31% and 16% in Arms 1 and 2, respectively. For both arms combined, the most common (≥10%) TRAEs were rashes and pruritus. In Arm 1, 8 pts (50%) and in Arm 2, 10 pts (53%) achieved stable disease (SD), with a mean duration of 18.4 (range: 14.0-30.3 wks) and 17.4 wks (range: 8.0-31.9 wks), respectively. PD effects were more evident in Arm 1 than Arm 2, including increased OX40 tumor expression and positive changes in gene signatures, reflecting an active anti-tumor immune response. Conclusions: PF-8600 was generally well tolerated and provided meaningful disease control. While safety and efficacy were not significantly different between the 2 doses, there were potential differences in the PD data. The safety and relative durability of SD in HCC pts may provide a rationale for exploration of combination therapy in this pt population. Clinical trial information: NCT02315066.