IPH5201, an anti-CD39 monoclonal antibody, as monotherapy or in combination with durvalumab in advanced solid tumors

Purpose: Blocking enzymatic activity of cluster of differentiation 39 (CD39) with IPH5201 may promote antitumor immunity by increasing immunostimulatory adenosine triphosphate and reducing immunosuppressive adenosine levels in the tumor microenvironment. This first-in-human, phase 1 study evaluated IPH5201 as monotherapy or in combination with durvalumab (anti-PD-L1) in patients with advanced solid tumors. Patients and Methods: The study consisted of two consecutive dose-escalation parts: IPH5201 monotherapy (100, 300, 1000 and 3000 mg) every 3 weeks (Q3W) and IPH5201 (300, 1000 and 3000 mg) + durvalumab 1500 mg Q3W. The primary endpoint was to evaluate safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics and immunogenicity. Results: Overall, 38 patients received IPH5201 monotherapy and 19 received IPH5201 + durvalumab, with median duration of follow-up 7.6 months (range, 1.0–23.7). The most common cancer types were pancreatic (42.1%), non-small-cell lung (19.3%), and colorectal (17.5%). The most common treatment-related adverse events (AEs) were infusion-related reactions and fatigue. There were no AE-related deaths and the maximum tolerated dose was not reached. Overall, 23/57 patients (40.4%) had stable disease as their best overall response. IPH5201 exhibited linear PK profile and estimated terminal half-life of 8 to 9 days at higher doses. On-treatment tumor biopsies revealed decreased CD39 ATPase activity in 5/7 patients, including all evaluable patients receiving the maximum dose of IPH5201 3000 mg Q3W. Conclusions: IPH5201 as monotherapy, or in combination with durvalumab, was well tolerated at pharmacologically active doses that induced reduction of intratumoral CD39 enzymatic activity and showed preliminary evidence for disease stabilization.