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

• Published in: Cancer immunology research 2016-11, Vol.4 (11_Supplement), p.B072-B072
• Main 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.
• Format: Article
• Language: English
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6066.IMM2016-B072

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 wa