Abstract B072: Phase Ib trial of the RNActive cancer vaccine BI 1361849 (CV9202) and local radiotherapy in patients with stage IV non-small cell lung cancer (NSCLC) with disease control after first-line chemotherapy or during therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: Updated clinical results and immune responses
Authors: Hipp M. M. , Sebastian M. , Weiss C. , Früh M. , Pless M. , Cathomas R. , Hilbe W. , Pall G. , Wehler T. , Alt J. , Bischoff H. , Geißler M. , Griesinger F. , Kollmeier J. , Papachristofilou A. , Doener F. , Fotin-Mleczek M. , Hong H. S. , Kallen K. J. , Klinkhardt U. , Koch S. D. , Niehus E. , Scheel B. , Schröder A. , Seibel T. , Gnad-Vogt U. , Zippelius A. 
Published: November 2016

Abstract
Background: Preclinical studies demonstrated that local radiotherapy (RT) acts synergistically with RNActive mRNA vaccines to enhance anti-tumor effects and increase tumor-infiltrating lymphocytes. BI 1361849 is a therapeutic vaccine comprising optimized mRNA constituents encoding six NSCLC-associated antigens. Interim data of a phase Ib study, employing local RT to increase the immune mediated tumor control by BI 1361849, have been previously published (J Clin Oncol 34, 2016, suppl; abstr e20627). Here we report results of immune response analyses as well as updated safety and efficacy data.
Methods: Patients (pts) with stage IV NSCLC were enrolled in three cohorts based on histological and molecular NSCLC subtypes (squamous and non-squamous cell with/without activating epidermal growth factor receptor (EGFR) mutations). Pts received two vaccinations with BI 1361849 before local RT to a single tumor lesion (thoracic, bone, lymph node, skin/subcutaneous) was administered in four consecutive daily fractions of 5 GY. Vaccination was continued until start of subsequent anti-cancer therapy. Maintenance pemetrexed (mP) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) were given in parallel according to the label where indicated. The primary endpoint was safety; secondary endpoints included objective response, progression-free survival (PFS) and overall survival (OS). Cellular and humoral immune responses were measured ex vivo by multifunctional intracellular cytokine staining, IFN-γ ELISpot, and ELISA in pre- and post-treatment blood samples.
Results: 26 pts were enrolled. 15 pts received mP, two received EGFR TKIs. Most frequent AEs were mild to moderate injection-site reactions and flu-like symptoms. No BI 1361849-related SAEs were reported. Based on preliminary data following up to 110 weeks of exposure, one confirmed PR was observed in a pt on mP, 13 pts (52%) experienced SD (8 pts on mP, 2 pts on EGFR-TKI and 3 pts without concomitant maintenance treatment, associated with 15% tumor shrinkage outside the radiation field in one pt without maintenance). 25 pts were available for immune response analysis. Preliminary data indicate that BI 1361849 was capable of eliciting antigen-specific immune responses in the majority of the patients including cellular and humoral immune responses.
Conclusion: BI 1361849 can be safely combined with local RT and mP treatment. Shrinkage of non-irradiated lesions and prolonged disease stablization was observed in a subset of pts, mainly in combination with mP. Data indicate immunogenicity of BI 1361849. Analyses of cellular and humoral immune responses will be presented, as well as updated clinical data.
Citation Format: M. M. Hipp, M. Sebastian, C. Weiss, M. Früh, M. Pless, R. Cathomas, W. Hilbe, G. Pall, T. Wehler, J. Alt, H. Bischoff, M. Geißler, F. Griesinger, J. Kollmeier, A. Papachristofilou, F. Doener, M. Fotin-Mleczek, H. S. Hong, K. J. Kallen, U. Klinkhardt, S. D. Koch, E. Niehus, B. Scheel, A. Schröder, T. Seibel, U. Gnad-Vogt, A. Zippelius. Phase Ib trial of the RNActive cancer vaccine BI 1361849 (CV9202) and local radiotherapy in patients with stage IV non-small cell lung cancer (NSCLC) with disease control after first-line chemotherapy or during therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: Updated clinical results and immune responses [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B072.