A multicenter, phase II study of soluble LAG-3 (Eftilagimod Alpha) in combination with pembrolizumab (TACTI-002) in patients with advanced non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC).

Julio Antonio Peguero Oncology Consultants PA, Department of Research, Houston, TX info_outline Julio Antonio Peguero, Pawan Bajaj, Enric Carcereny, Timothy Dudley Clay, Bernard Doger, Enriqueta Felip, Matthew Krebs, Martin Forster, Santiago Ponce Aix, Patricia Roxburgh, Frederic Triebel

Authors Julio Antonio Peguero Oncology Consultants PA, Department of Research, Houston, TX info_outline Julio Antonio Peguero, Pawan Bajaj, Enric Carcereny, Timothy Dudley Clay, Bernard Doger, Enriqueta Felip, Matthew Krebs, Martin Forster, Santiago Ponce Aix, Patricia Roxburgh, Frederic Triebel Organizations Oncology Consultants PA, Department of Research, Houston, TX, Griffith University, Brisbane, Australia, Badalona-Hospital Germans Trias i Pujol, Badalona, Spain, St. John of God Hospital, Perth, Australia, START Madrid Fundacion Jimenez Diaz, Madrid, Spain, Hospital Universitari Vall d'Hebron, Barcelona, Spain, The Christie NHS Foundation Trust and The University of Manchester, Manchester Academic Health Sciences Centre, Manchester, United Kingdom, The Christie NHS Foundation Trust, London, United Kingdom, Hospital 12 de Octubre, Madrid, Spain, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom, Immutep SAS, Orsay Cedex, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Eftilagimod alpha (efti, IMP321) is a recombinant LAG-3Ig fusion protein that binds to MHC class II and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. Pembrolizumab binds to the PD-1 receptor, blocking both immune-suppressing ligands, PD-L1 and PD-L2, from interacting with PD-1 to help restore effector T-cell responses. The rationale to combine efti and pembrolizumab comes from their complementary mechanisms of action. Efti activates APCs and lead to an increase in activated T cells which effect potentially reduces the number of non-responders to pembrolizumab. Combining an APC activator like efti to pembrolizumab is therefore fundamentally different from many other trials combining two checkpoint inhibitors like an anti-LAG-3 mAb with an anti-PD-1 mAb. In a previous phase I study (NCT 02676869) in metastatic melanoma the combination was found to be safe and well tolerable with encouraging signs of clinical activity. Methods: In the course of this multicenter, open label, Phase II study, patients will be recruited for each of three indications: A: 1st line, PD-X (PD-1 or PD-L1) naïve non-small cell lung cancer (NSCLC); B: 2nd line, PD-X refractory NSCLC; C: 2nd line PD-X naive head and neck squamous cell carcinoma (HNSCC). The study is designed according to Simon's optimal two-stage design, with objective response rate acc to iRECIST as primary endpoint. Secondary endpoints include progression free survival and overall survival. In case there are more responses achieved than a predefined threshold (each part counted separately) in pts recruited in the initial stage (n = 58), additional pts (51) will be recruited in stage 2. Efti will be administered for a maximum of 18 cycles (1 cycle = 3 weeks) as 30 mg subcutaneous injection every 2 weeks for the first 8 and every 3 weeks for the 10 following cycles. Pembrolizumab (200 mg intravenous infusion every 3 weeks) is administered in parallel for up to 35 cycles. Patients are followed up for progression and survival. Clinical trial information: 03625323.