Safety and activity of M7824, a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients with HPV associated cancers.

• DOI: 10.1200/jco.2018.36.15_suppl.3007
• Publication Date: 2018-09-05T10:24:10Z
• Authors: Julius Strauss; Margaret Elena Ga...; Jason Redman; Ravi Amrit Madan; Elizabeth Lamping; Michell Manu; Andrea Burmeister; Jennifer L. Marte; Lisa M. Cordes; Laureen Ojalvo; Christoph Helwig; Jeffrey Schlom; James L. Gulley
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

3007 Background: Therapies targeting PD-1/L1 have produced response rates of 15-20% in patients (pts) with HPV associated cancers (HAC) including cervical (cerv), anal or head and neck squamous cell carcinoma (HNSCC). Another potential target for these diseases is transforming growth factor-β (TGF-β) as genome wide association studies HPV+ shown TGF-β to be significantly overexpressed. M7824 a bifunctional fusion protein PD-L1 comprised human IgG1 monoclonal antibody against fused 2 extracellular domains receptor II, which functions "trap". We report data from pts HAC on fully enrolled dose escalation portion phase 1 trial M7824. Methods: NCT02517398 1, 3+3 dose-escalation study. Pts received at 3, 10, 20, 30 mg/kg Q2W until PD unacceptable toxicity. The primary objective was safety maximum tolerated (MTD). A key secondary best overall per RECIST v1.1. Results: As Feb 5 2018, 16 (9 cerv, 4 3 HNSCC) were enrolled. + 11 unknown (uk) pts. Grade treatment related adverse events (TRAEs) occurred 3/16 (colitis, cystitis, gastroparesis; all cerv). Notably also had disease reduction. hypokalemia accompanied the gastroparesis. No other grade 4-5 TRAEs seen. only DLT colitis (at 20 mg/kg) no MTD reached. 9/16 (56%) reduction pt (cerv; HPV+) durable CR, (2 HNSCC, anal; PRs, uk) an unconfirmed PR, cerv; both near PRs (-25%, -27%) (anal; modest (-9%). In all, 6/16 (37.5%) ongoing responses, 5/6 confirmed. Of known disease, 5/11 (45.5%) confirmed responses. Conclusions: Data suggests manageable profile ORR 37.5% 45.5% disease. promising drug continues evaluated I II trials. Clinical information: NCT02517398.