Abstract 1010P
Background
CV8102 is a non-coding, non-capped RNA complexed with a carrier peptide activating the innate (via TLR7/8, RIG-I) and adaptive immune system. An ongoing phase I trial (CV-8102-008) is investigating it. CV8102 either as a single agent or in combination with systemic anti-PD-1 antibodies in patients with advanced cutaneous melanoma (cMEL), squamous cell carcinoma of the skin (cSCC) or head and neck (hnSCC) and adenoid cystic carcinoma (ACC). The dose escalation part of this study has been completed, and preliminary results from this part are reported here.
Methods
Study CV-8102-008 is an open-label, cohort-based, dose escalation and expansion phase I study. Eight intratumoral injections of CV8102 are being administered initially over a 12-week period. Primary objective of the dose-escalation part is to determine the maximum tolerated dose and recommended phase II dose.
Results
As of February 5, 2021, 33 patients have been treated with CV8102 as a single agent (25-900 μg) and 25 patients have received CV8102 (25-900 μg) in combination with anti-PD-1 antibodies. At CV8102 dose levels of 25 μg 600 μg no dose limiting toxicities were reported in the single agent and anti PD-1 combination cohorts. At the 900 μg dose level (single agent) 1 out of 6 patients experienced a dose limiting toxicity (transient G3 transaminase increase in the context of G2 CRS) after the second injection of CV8102. Based on recommendation of the DMC, a dose of 600 μg was determined as recommended phase II dose for both, monotherapy and combination therapy. Overall, most frequent treatment emergent adverse events were mild to moderate fatigue, fever, headache or chills. Regression of injected and distant noninjected lesions was observed in several patients in the single agent (including 1 CR and 2 PRs) and the anti-PD-1 combination cohorts (including 1 PR per RECIST 1.1.). Updated safety and efficacy results will be presented.
Conclusions
CV8102 showed an acceptable safety profile and preliminary evidence of clinical efficacy as single agent and in combination with anti-PD-1-antibodies.
Clinical trial identification
NCT03291002.
Editorial acknowledgement
Legal entity responsible for the study
CureVac AG.
Funding
CureVac AG.
Disclosure
T. Eigentler: Financial Interests, Institutional, Principal Investigator, Local PI: 4SC; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Amgen; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Coordinating PI: CureVac; Financial Interests, Institutional, Principal Investigator, Coordinating PI: GenenTech; Financial Interests, Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis. L. Heinzerling: Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: CureVac; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Principal Investigator: BMS; Financial Interests, Institutional, Principal Investigator: MSD; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Roche; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: GSK; Financial Interests, Institutional, Principal Investigator: CureVac; Financial Interests, Institutional, Principal Investigator: Immunocore; Financial Interests, Institutional, Principal Investigator: Novartis. J. Krauss: Non-Financial Interests, Principal Investigator: BioNtech; Non-Financial Interests, Principal Investigator: CureVac; Non-Financial Interests, Principal Investigator: Vaccibody. C. Weishaupt: Financial Interests, Personal, Invited Speaker: Bristol Meyer-Squibb; Financial Interests, Personal, Advisory Board: Bristol Meyers-Squibb; Financial Interests, Personal, Advisory Board, and support for congress fees: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche Pharma; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Other, Support for congress fees: Sun Pharma. S. Ochsenreither: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: CureVac; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Licensing Fees, Patent of T-cell therapy target: Fred Hutchinson Cancer Research Center. C. Lebbe: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Funding, No Financial Interest: BMS; Financial Interests, Personal, Funding, No Financial Interest: Roche; Non-Financial Interests, Advisory Role: Amgen; Non-Financial Interests, Advisory Role: BMS; Non-Financial Interests, Advisory Role: Merck Serono; Non-Financial Interests, Advisory Role: MSD; Non-Financial Interests, Advisory Role: Novartis; Non-Financial Interests, Advisory Role: Pierre Fabre; Non-Financial Interests, Advisory Role: Roche; Non-Financial Interests, Advisory Role: Sanofi; Other, Other, Honoraria, Speaker's Bureau: Amgen; Other, Other, Honoraria, Speaker's Bureau, Travel, Accommodations, Expenses: BMS; Other, Other, Honoraria: Incyte; Other, Other, Honoraria, Speaker’s Bureau, Travel, Accommodations, Expenses: MSD; Other, Other, Honoraria, Speaker's Bureau, Travel, Accommodations, Expenses: Novartis; Other, Other, Honoraria: Pfizer; Other, Other, Honoraria, Travel, Accommodations, Expenses: Pierre Fabre; Other, Other, Honoraria, Speaker's Bureau: Roche; Other, Other, Travel, Accommodations, Expenses: Sanofi. P. Mohr: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Bristol-Myers; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Funding: Novartis; Non-Financial Interests, Principal Investigator: Bristol-Myers Squibb; Non-Financial Interests, Principal Investigator: Merck Sharp & Dohme. M. Oliva: Financial Interests, Personal, Other, Podcast: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS. P. Terheyden: Financial Interests, Personal, Advisory Board: BMS, Novartis, Pierre-Fabre, Merck Serono, Sanofi, Roche, Kyowa Kirin; Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Pierre-Fabre, CureVac, Roche, Kyowa Kirin, Biofrontera; Financial Interests, Personal, Other, Travel support: BMS, Pierre-Fabre. J.M. Trigo Perez: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker, Travel grant: MSD; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Institutional, Research Grant, No Financial Interest: BMS; Non-Financial Interests, Advisory Role: BMS; Non-Financial Interests, Advisory Role: Merck. C. Robert: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca. E. Richtig: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Principal Investigator, Local PI, No Financial Interest: Amgen; Financial Interests, Principal Investigator, Local PI, No Financial Interest: BMS; Financial Interests, Principal Investigator, Local PI, No Financial Interest: Curevac; Financial Interests, Principal Investigator, Coordinating PI, No Financial Interest: Delcath; Financial Interests, Principal Investigator, Local PI, No Financial Interest: Incyte; Financial Interests, Other, Subinvestigator, No Financial Interest: Merck; Financial Interests, Leadership Role, Local PI, No Financial Interest: MSD; Financial Interests, Other, Steering Committee Member, No Financial Interest: Novartis; Financial Interests, Principal Investigator, Coordinating PI, No Financial Interest: Novartis; Financial Interests, Principal Investigator, Coordinating PI, No Financial Interest: Pierre Fabre; Financial Interests, Principal Investigator, Local PI, No Financial Interest: Roche; Financial Interests, Other, Named Patient Program, No Financial Interest: Sanofi; Non-Financial Interests, Invited Speaker, President Of The Austrian Cancer Aid/Styria, A Non-Profit Organization: Austrian Cancer Aid/Styria. A. Soria: Financial Interests, Personal, Invited Speaker: Novartis Pharma, MSD, BMS, Pierre Fabre, Sanofi Aventis, Merck Serono; Financial Interests, Personal, Speaker's Bureau: Novartis Pharma, MSD, BMS, Pierre Fabre, Sanofi Aventis, Merck Serono; Financial Interests, Personal, Advisory Board: Novartis Pharma, MSD, BMS, Pierre Fabre, Sanofi Aventis, Merck Serono; Financial Interests, Personal, Expert Testimony: Novartis Pharma, MSD, BMS, Pierre Fabre, Sanofi Aventis, Merck Serono; Non-Financial Interests, Personal and Institutional, Principal Investigator: Novartis Pharma, MSD, BMS, Pierre Fabre. S. Kays: Financial Interests, Personal, Full Or Part-Time Employment: Curevac AG; Financial Interests, Personal, Stocks/Shares: Curevac AG. B. Schmitt-Bormann: Financial Interests, Personal, Full Or Part-Time Employment: Curevac. M. Falk: Financial Interests, Institutional, Full Or Part-Time Employment: Curevac. U.S. Gnad-Vogt: Financial Interests, Personal, Full Or Part-Time Employment: Curevac; Financial Interests, Personal, Stocks/Shares: Curevac. All Other Authors Have Declared No Conflicts Of Interest.