Abstract B209: Phase 1/2 study of mRNA vaccine therapy + durvalumab (durva) ± tremelimumab (treme) in patients with metastatic non-small cell lung cancer (NSCLC)
Authors: Sabari Joshua , Ramirez Kristen Aufiero , Schwarzenberger Paul , Ricciardi Toni , Macri Mary , Ryan Aileen , Venhaus Ralph 
Published: February 2019

Abstract
Vaccine therapies stimulate the immune system to attack cancer cells (active immunotherapy), whereas checkpoint inhibitors block immune inhibition (passive immunotherapy). BI 1361849 (formerly CV9202) is a cancer vaccine comprising 6 mRNA constituents, each of which encodes for one of the non-small cell lung cancer (NSCLC) associated antigens: MUC1, survivin, NY-ESO-1, 5T4, MAGE-C2, and MAGE-C1. Durvalumab (durva) is a checkpoint inhibitor that blocks programmed cell death ligand-1 (PD-L1) binding to programmed cell death-1 (PD-1). Several PD-1 and PD-L1 blocking antibodies are approved for NSCLC. Tremelimumab (treme) is an anti-cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) blocking antibody. Targeting both the CTLA-4 and PD-1 checkpoint pathways provides the potential for additive or synergistic effects. This study combines active and passive immunotherapies to determine if the addition of a mRNA vaccine, BI 1361849, can enhance the activity of checkpoint blockade. This ongoing phase 1/2, open-label study (NCT03164772) evaluates the safety and efficacy of BI 1361849 when administered with durva (Arm A) or durva + treme (Arm B) in patients with NSCLC. In Arm A, an initial dose evaluation phase follows a 3+3 design to confirm the dose of durva (full dose 1500 mg or de-escalated 750 mg, if needed) to be given with the vaccine. Arm B uses the dose established in Arm A, with the addition of 75 mg treme. In the expansion phase, 20 patients are treated in each arm. To aid in the evaluation of immune responses, there is an additional control group (n=10), in which patients receive the checkpoint inhibitor(s) only. Study treatment is administered over 12 cycles (28 days each). Durva (x 12 doses) and treme (x 4 doses, Arm B only) are administered intravenously every 28 days. The vaccine is administered as a total of 14 doses (of the 6 components) during the 12 cycles, using a device that provides a needle-free intradermal administration. The primary endpoint is assessment of safety and tolerability, including evaluation of dose-limiting toxicities. Secondary endpoints include progression-free survival and objective response rate at 8 and 24 weeks, disease control rate, response duration, and overall survival, with tumor response evaluated by RECIST 1.1 and immune-related RECIST. Exploratory objectives include effects on tumor microenvironment and evaluation of immune responses. Enrollment opened 20 December 2017. As of 27 June 2018, 2 patients are enrolled; enrollment is ongoing.
Citation Format: Joshua Sabari, Kristen Aufiero Ramirez, Paul Schwarzenberger, Toni Ricciardi, Mary Macri, Aileen Ryan, Ralph Venhaus. Phase 1/2 study of mRNA vaccine therapy + durvalumab (durva) ± tremelimumab (treme) in patients with metastatic non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B209.