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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4988 - Phase I dose-escalation and expansion study of intratumoral CV8102, a RNA-based TLR- and RIG-1 agonist in patients with advanced solid tumors

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Patrick Terheyden

Citation

Annals of Oncology (2018) 29 (suppl_8): viii442-viii466. 10.1093/annonc/mdy289

Authors

P. Terheyden1, C. Weishaupt2, L. Heinzerling3, U. Klinkhardt4, J. Krauss5, P. Mohr6, F. Kiecker7, J.C. Becker8, A. Dähling (Submitter)4, F. Döner9, R. Heidenreich9, B. Scheel4, O. Schönborn-Kellenberger10, T. Seibel4, U. Gnad-Vogt4

Author affiliations

  • 1 Klinik Für Dermatologie, Allergologie Zund Venerologie, Universitätsklinikum Schleswig-Holstein, 23538 - Lübeck/DE
  • 2 Haut- Und Geschlechtskrankheiten, Universitätsklinikum Münster (UKM), 48149 - Münster/DE
  • 3 Dermatologie, Universitätsklinikum Erlangen, 91054 - Erlangen/DE
  • 4 Clinical Development, CureVac AG, 60325 - Frankfurt am Main/DE
  • 5 Onkologie, Universitätsklinikum Heidelberg (NCT), 69120 - Heidelberg/DE
  • 6 Dermatologie, Elbe Klinikum Buxtehude, 21614 - Buxtehude/DE
  • 7 Dermatologie, Charité Universitätsmedizin Berlin, 10117 - Berlin/DE
  • 8 Dermatologie, Universitätsklinikum Essen, 45147 - Essen/DE
  • 9 Research, CureVac AG, 72076 - Tübingen/DE
  • 10 Statistical Consulting, Cogitars GmbH, 69115 - Heidelberg/DE
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Resources

Abstract 4988

Background

Local activation of innate immune signaling pathways, such as Toll-like Receptors (TLRs) or RIG-I-like Receptors (RLRs), is a promising cancer immunotherapeutic approach to overcome the tumor immunosuppressive microenvironment and to induce/restore anti-tumor immunity. CV8102 consists of a single-stranded, non-coding RNA complexed with a cationic peptide and acts as an agonist to human TLR-7, -8 and RLRs. Local administration of CV8102 was shown to induce upregulation of inflammatory cytokines, chemokines and IFN-y related genes at the injection site followed by activation of T, NK, NKT cells and migratory dendritic cells in the draining lymph node (Heidenreich 2015; Ziegler 2017). In a syngeneic murine model, intratumoral (IT) delivery of CV8102 induced dose-dependent anti-tumor activity and synergized with systemic anti-PD1 antibody treatment.

Trial design

This phase I study is evaluating IT injection of CV8102 alone or in combination with a systemic anti-PD-1 antibody in patients with advanced solid tumors. Patients with advanced inoperable melanoma, cutaneous/head and neck squamous cell or adenoid cystic carcinoma and at least one lesion accessible for IT injection are eligible. After determination of the maximum tolerated/ recommended dose of CV8102 alone and in combination with an anti-PD1 antibody, expansion cohorts are planned in different indications. A Bayesian logistic regression model with overdose control will be used to guide the dose escalation. Patients in each cohort will receive up to 8 injections into a single tumor lesion over a 12 weeks period. The primary objective is to determine safety and tolerability, secondary/explorative objectives are to evaluate tumor response and changes in tumor tissue and blood-based biomarkers. The study has been initiated and enrollment is ongoing.

Clinical trial identification

NCT03291002.

Legal entity responsible for the study

CureVac AG, Paul-Ehrlich-Str. 15, 72076 Tübingen, Germany.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

P. Terheyden: Honoraria, Travel expenses: Novartis, Merck, Roche, BMS, Biofrontera; Advisory board: Roche, BMS, Sanofi Novartis, Merck. L. Heinzerling: Consultant: CureVac AG PI in clinical study at site Erlangen. P. Mohr: Consultant or advisory role: Merck, Roche, GSK, BMS, Novartis, SciBase, LEO; Honoraria: GSK, Roche, Merck, BMS, Novartis, LEO, SciBase; Research funding: Merck. F. Kiecker: Payments, Travel grants for symposia, Advisory boards, Meetings: Amgen, BMS, Merck-Serono, MSD, Novartis, Pierre-Fabre, Regeneron, Roche. J.C. Becker: Speaker honoraria: Amgen, MerckSerono and Pfizer; Advisory board honoraria: Amgen, CureVac, eTheRNA, Lytix, MerckSerono, Novartis, Rigontec, Takeda; Research funding: Boehringer Ingelheim, BMS, MerckSerono. U. Gnad-Vogt: Stock, Other ownership interests: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

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