Data from IPH5201, an Anti-CD39 mAb, as Monotherapy or in Combination with Durvalumab in Advanced Solid Tumors

<div>AbstractPurpose:<p>Blocking enzymatic activity of cluster of differentiation 39 (CD39) with IPH5201 may promote antitumor immunity by increasing immunostimulatory ATP 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.</p>Patients and Methods:<p>The study consisted of two consecutive dose-escalation parts: IPH5201 monotherapy (100, 300, 1,000, and 3,000 mg) every 3 weeks and IPH5201 (300, 1,000, and 3,000 mg) + durvalumab 1,500 mg every 3 weeks. The primary endpoint was to evaluate safety and tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, and immunogenicity.</p>Results:<p>Overall, 38 patients received IPH5201 monotherapy and 19 received IPH5201 + durvalumab, with a median duration of follow-up of 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%) cancers. The most common treatment-related adverse events were infusion-related reactions and fatigue. There were no adverse event–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 a linear pharmacokinetic profile and an 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 3,000 mg every 3 weeks.</p>Conclusions:<p>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.</p>Significance:<p>The adenosine pathway is a source of emerging targets in cancer immunotherapy. IPH5201 is a mAb that targets the adenosine pathway by blocking human CD39 enzymatic activity. In this first-in-human, phase 1 study, IPH5201 as monotherapy or in combination with durvalumab was well tolerated with a manageable safety profile in patients with advanced solid tumors. Preliminary evidence for disease stabilization and reduction of tumoral CD39 enzymatic activity were observed.</p></div>