First in human (FIH) study of an OX40 agonist monoclonal antibody (mAb) PF-04518600 (PF-8600) in adult patients (pts) with select advanced solid tumors: Preliminary safety and pharmacokinetic (PK)/pharmacodynamic results.

3079 Background: Stimulating effector T cells is an attractive anti-cancer therapeutic strategy. PF-8600 is a novel fully human IgG2 agonistic mAb specific for human OX40, a tumor necrosis factor receptor expressed primarily on activated T cells. PF-8600 provides an immunotherapeutic approach distinct to PD-1 and CTLA-4. A FIH phase 1 study of PF-8600 to investigate the safety, maximum-tolerated dose, PK, immunomodulation and preliminary antitumor activity is on-going in pts with refractory melanoma, head and neck squamous cell, renal cell and hepatocellular carcinoma. Methods: PF-8600 was administrated intravenously every 14 days at doses 0.01 - 0.3 mg/kg. 28-day dose-limiting toxicity (DLT) was evaluated using a modified Toxicity Probability Interval design. PF-8600 PK profiling was completed during cycles 1 and 3. Starting at 0.1 mg/kg, each dose level is expanded to 10 patients for paired tumor biopsy assessments. Free and total OX40 receptor and markers of T cell proliferation (Ki67) were measured on CD4 and CD8 naïve, central and effector memory cells. Results: As of 02 Nov 2015, 9 pts were enrolled in the dose-escalation phase of the study: 0.01 mg/kg (2pts), 0.1 mg/kg (3 pts) and 0.3 mg/kg (4pts). No DLT, drug-related serious Adverse Events (AEs), immune related AEs or drug-related grade 3-5 AEs were observed. The most frequent drug-related AE was grade 2 fatigue (33.3%). 4 patients experienced best ORR of stable disease (RECIST), and 2 previously immunotherapy-treated patients have been on study for > 6 months. In the periphery, PF-8600 exhibited full target receptor occupancy and enhanced memory T cell proliferation at 0.3 mg/kg. Exposure (AUCτ ) increased with increasing doses during cycle 1. Conclusions: These preliminary results demonstrate that PF-8600, an agonistic OX40 mAb, is safe up to 0.3 mg/kg, and biomarker endpoints are met. The highest planned dose cohorts (1.5 and 3 mg/kg) are enrolling and will be presented. Clinical trial information: NCT02315066.