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
Author Info: (1) Clinic of Radiotherapy and Radiation Oncology, University Hospital Basel, Basel, Switzerland. (2) CureVac AG, Tubingen, Germany. (3) CureVac AG, Tubingen, Germany. (4) Hospital
Author Info: (1) Clinic of Radiotherapy and Radiation Oncology, University Hospital Basel, Basel, Switzerland. (2) CureVac AG, Tubingen, Germany. (3) CureVac AG, Tubingen, Germany. (4) Hospital of St Gallen, St Gallen and University of Bern, Bern, Switzerland. (5) University Hospital Frankfurt, Frankfurt, Germany. (6) University Hospital Frankfurt, Frankfurt, Germany. (7) Cantonal Hospital of Winterthur, Winterthur, Switzerland. (8) Hospital Graubunden, Chur, Switzerland. (9) Medical Department, Center for Oncology and Hematology, Wilhelminenspital, Wien, Austria. (10) University Hospital Innsbruck, Innsbruck, Austria. (11) Department of Internal Medicine III, University Medical Center Mainz, Mainz, Germany. (12) Department of Internal Medicine III, University Medical Center Mainz, Mainz, Germany. (13) Thoraxklinik Heidelberg gGmbH, Heidelberg, Germany. (14) Klinik fur Allg Innere Medizin, Onkolologie/ Hamatologie, Gastroenterologie, Infektiologie, Esslingen, Germany. (15) Department Hematology and Oncology, Pius Hospital University, Oldenburg, Germany. Department Internal Medicine-Oncology, Medical Campus University of Oldenburg, Oldenburg, Germany. (16) eTheRNA Immunotherapies NV, Niel, Belgium. (17) CureVac AG, Tubingen, Germany. (18) CureVac AG, Tubingen, Germany. (19) CureVac AG, Tubingen, Germany. (20) CureVac AG, Tubingen, Germany. (21) CureVac AG, Tubingen, Germany. (22) CureVac AG, Tubingen, Germany. (23) CureVac AG, Tubingen, Germany. (24) CureVac AG, Tubingen, Germany. (25) CureVac AG, Tubingen, Germany. (26) CureVac AG, Tubingen, Germany. (27) Medical Oncology, University Hospital Basel, Basel, Switzerland. Alfred.Zippelius@usb.ch.
