In a phase 1b clinical trial, BI1361849 – made up of sequence-optimized mRNA encoding six NSCLC-associated antigens formulated with protamine – was tested in combination with local radiation in 26 stage IV NSCLC patients who had PR or SD following first-line therapy; 73% of patients continued on second-line maintenance treatment. Treatment was well tolerated and 84% of patients showed antigen-specific humoral and/or cellular immune responses against one or more BI1361849 antigens. One patient achieved partial response, 46% of patients achieved stable disease, and shrinking of some non-irradiated lesions was observed.
BACKGROUND: Preclinical studies demonstrate synergism between cancer immunotherapy and local radiation, enhancing anti-tumor effects and promoting immune responses. BI1361849 (CV9202) is an active cancer immunotherapeutic comprising protamine-formulated, sequence-optimized mRNA encoding six non-small cell lung cancer (NSCLC)-associated antigens (NY-ESO-1, MAGE-C1, MAGE-C2, survivin, 5T4, and MUC-1), intended to induce targeted immune responses. METHODS: We describe a phase Ib clinical trial evaluating treatment with BI1361849 combined with local radiation in 26 stage IV NSCLC patients with partial response (PR)/stable disease (SD) after standard first-line therapy. Patients were stratified into three strata (1: non-squamous NSCLC, no epidermal growth factor receptor (EGFR) mutation, PR/SD after >/=4 cycles of platinum- and pemetrexed-based treatment [n = 16]; 2: squamous NSCLC, PR/SD after >/=4 cycles of platinum-based and non-platinum compound treatment [n = 8]; 3: non-squamous NSCLC, EGFR mutation, PR/SD after >/=3 and