ESMO 2017: Results of the randomized, placebo-controlled phase I/IIB trial of CV9104, an mRNA based cancer immunotherapy, in patients with metastatic castration-resistant prostate cancer (mCRPC)

Madrid, Spain ( Dr. Stenzl and colleagues from Germany presented results of their phase I/IIB trial assessing the mRNA based cancer immunotherapy CV9104 for patients with metastatic castration-resistant prostate cancer (mCRPC) at today’s poster session at ESMO 2017.

CV9104 is a novel prostate cancer immunotherapy based on sequence-optimized, free and protamine-complexed mRNA encoding the antigens PSA, PSMA, PSCA, STEAP1, PAP and MUC1. Safety and immune responses to the predecessor therapy CV9103 encoding 4 of the antigens have been previously described [1]. The objective of this study was to assess whether immunotherapy with CV9104 in addition to standard of care results in longer overall survival (OS) than placebo plus standard of care in patients with mCRPC.

After completion of a safety lead-in phase I, 197 men with chemo-naïve, oligosymptomatic/asymptomatic mCRPC without visceral metastases were randomized 2:1 to intradermal CV9104 or placebo. Double-blinded treatment was continued beyond initial progression until progression under first subsequent standard of care therapy or toxicity. The primary endpoint was OS. Key secondary end points included radiographic progression-free survival (rPFS1/rSPFS from randomization until initial progression/second progression on standard of care therapy and rPFS2 from start of standard of care therapy to second progression), time to symptom progression and cellular and humoral immune responses.

There were 134 patients randomized to CV9104 and 63 to placebo. Patient characteristics, median number of administrations and first subsequent standard of care therapies were well balanced between the arms. No significant difference in OS was found: median OS was 35.5 months [95%CI 28.0-NE] in the CV9104 arm vs. 33.7 months [95%CI 28.7-NE] in the placebo arm (hazard ratio [HR] 1.1, 95%CI 0.70-1.76). There were also no significant differences in the rPFS endpoints and time to symptom progression. Incidence of Grade ≥3 adverse events (51.1% vs. 59.7%) and serious adverse events (44.5% vs. 43.5%) was similar in both arms. Injection site reactions and flu like symptoms were more frequent in the CV9104 arm.

In summary, the results of this phase I/IIB trial demonstrated that CV9104 did not improve OS compared to placebo in mCRPC. Cancer-mediated immunosuppression, tolerance to the prostate cancer self-antigens and a suboptimal mode of administration for this protamine formulated mRNA vaccine may have contributed to this outcome. Further development of mRNA based cancer immunotherapies is ongoing with focus on improved formulations, modes of administration and combination with checkpoint blocking antibodies.

Speaker: Arnulf Stenzl, University of Tubingen, Tübingen, Germany

Co-Authors: S. Feyerabend (Reutlingen, Germany) I. Syndikus (Bebington, United Kingdom) T. Sarosiek (Warsaw, Poland) H. Kübler (Würzburg, Germany) A. Heidenreich (Köln, Germany) R. Cathomas (Chur, Switzerland) C. Grüllich (Heidelberg, Germany) Y. Loriot (Villejuif, France) J. Perez Gracia (Pamplona, Spain) U. Klinkhardt (Frankfurt, Germany) A. Schroeder (Frankfurt, Germany) O. Schönborn-Kellenberger (Heidelberg, Germany) V. Reus (Frankfurt, Germany) V. Reus (Frankfurt, Germany) S. Koch (Tübingen, Germany) H. Hong (Tübingen, Germany) T. Seibel (Frankfurt, Germany) K. Fizazi (Villejuif, France) U. Gnad-Vogt (Frankfurt, Germany)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain


Kubler H, Scheel B, Gnad-Vogt U, et al. Self-adjuvanted mRNA vaccination in advanced prostate cancer patients: A first-in-man phase I/IIa study. J Immunother Cancer 2015;3:26

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