Abstract CT225: A Phase Ib/IIa randomized pilot study to investigate the safety and tolerability of autologous T-cells with enhanced T-cell receptors specific to NY-ESO-1/LAGE-1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non-small cell lung cancer

Introduction: There is a high unmet medical need for patients with advanced non-small cell lung cancer (NSCLC) who have failed platinum-based chemotherapy and checkpoint inhibitors. Only 10% of such patients receive any benefit from current therapies, and novel therapies are needed to improve outcomes. Preclinical data support the efficacy, specificity and possible safety of NYESO1/LAGE1a T-cell receptor-engineered patient Tcells (GSK3377794) in NSCLC. Pembrolizumab (PEM) is a monoclonal antibody, which specifically blocks PD1/PDL1 interaction, thereby increasing the antitumor function of Tcells. Thus, the combination of GSK3377794 and PEM may work synergistically due to the inhibition of PD1/PD-L1 signaling on GSK3377794 and other T-cells, potentially further improving the therapeutic effect. Methods: This is a Phase Ib/IIa randomized, multiarm, openlabel pilot study (NCT03709706) in human leukocyte antigen (HLA)A*02:01, HLAA*02:05 and/or HLAA*02:06 adult patients (aged >18 years) whose tumors express NYESO1 and/or LAGE1a. This study aims to enroll up to 44 patients with unresectable Stage IIIb or Stage IV NSCLC who were either ineligible for definitive chemoradiotherapy, have recurrent disease which has progressed during or after platinumbased chemotherapy with or without anti-PD-1 agents, have terminated prior treatment due to intolerable side effects, or have refused standard approved treatment. Patients will be randomized (1:1) to two treatment arms. Arm A will receive GSK3377794 as monotherapy, administered as a single intravenous (IV) infusion; Arm B will receive GSK3377794 as a single IV infusion on Day 1 followed by PEM 200 mg initiated on Day 22 and continued for up to 35 cycles or until disease progression. Patients in Arm A who progress after receiving GSK3377794 monotherapy will be offered antiPD1 therapy at the same dose and duration as Arm B. The study will use a Bayesian adaptive design, wherein enrollment can be halted in either arm for futility. The patient journey will consist of 3 parts: patients will undergo eligibility screening (Part 1), followed by leukapheresis (Part 2), after which patients will enter the Interventional Phase (Part 3) during which patients will receive preparative lymphodepleting chemotherapy followed by infusion of GSK3377794. The first patient was screened on December 31, 2018. ClinicalTrials.gov identifier: NCT03709706 Study is funded by GlaxoSmithKline and is in collaboration with Merck & Co., Inc. Citation Format: Karen L. Reckamp, Wallace Akerley, Martin J. Edelman, Balazs Halmos, Kai He, Melissa Johnson, Raja Mudad, Joel W. Neal, Taofeek K. Owonikoko, Jyoti D. Patel, Sandip P. Patel, Jonathan W. Riess, Adrian G. Sacher, Simon Turcotte, Liza C. Villaruz, Marjorie G. Zauderer, Benedetto Farsaci, Aisha Hasan, Roma Patel, Yuehui Wu, Michael Chisamore, Vincent Lam. A Phase Ib/IIa randomized pilot study to investigate the safety and tolerability of autologous T-cells with enhanced T-cell receptors specific to NY-ESO-1/LAGE-1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT225.