3305 - A phase I dose-escalation and expansion trial of intratumorally administered CV8102, alone and in combination with anti-PD-1 in patients with advanced solid tumors

Background

Intratumoral injection of immunomodulating agents is a promising approach to prime antitumor immune responses and to control tumor growth while avoiding major systemic toxicities. Intratumoral CV8102, a TLR7/8/RIG-1 agonist based on noncoding single stranded RNA showed dose dependent single agent activity and synergism with PD-1 blockade in preclinical models.

Trial design

CV-8102-008 (NCT03291002) is a phase I, open-label, dose escalation and expansion study of intratumoral CV8102 in patients with advanced, inoperable cutaneous melanoma (cMEL), squamous cell carcinoma of the skin (cSCC) or head and neck (hnSCC) or adenoid cystic carcinoma (ACC). Eight intratumoral injections of CV8102 are provided over a 12 weeks period, unless disease progression requiring initiation of next-line therapy or unacceptable toxicity occurs. Patients showing evidence of clinical benefit on single agent CV8102 are eligible for further treatment. Currently the first part of the trial, with escalating doses of single agent CV8102 and CV8102 in combination with anti-PD-1 antibodies to determine the maximum tolerated/ recommended dose (MTD/RCD) guided by a Bayesian logistic regression model with overdose control. and flexible cohort sizes is ongoing. Safety, biological and tumor response according to RECIST 1.1/ir RECIST of CV8102 alone/in combination with anti-PD-1 antibodies will be further characterized in expansion cohorts including anti-PD-1 naïve and refractory patients.

Clinical trial identification

NCT03291002.

Editorial acknowledgement

Legal entity responsible for the study

CureVac AG.

Funding

CureVac AG.

Disclosure

J. Krauss: Advisory / Consultancy: Vaccibody; Advisory / Consultancy: Zelluna; Research grant / Funding (self): Heidelberg ImmunoTherapeutics. T. Eigentler: Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb. C. Weishaupt: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: CureVac; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: La Roche Posay; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Leo Pharma; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda. P. Terheyden: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Merck Serono; Honoraria (self): CureVac. L. Heinzerling: Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD; Advisory / Consultancy: BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: CureVac; Advisory / Consultancy: Pierre-Fabre; Advisory / Consultancy: Sanofi. P. Mohr: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Pierre Fabre; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: Merck; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Roche; Advisory / Consultancy, Shareholder / Stockholder / Stock options: GSK; Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: BMS; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Novartis; Advisory / Consultancy: LEO; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Amgen. B. Weide: Advisory / Consultancy: CureVac GmbH; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy, Research grant / Funding (self): MSD. S. Ochsenreither: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: CureVac; Honoraria (self), Advisory / Consultancy: Glenmark; Honoraria (self), Advisory / Consultancy: Incyte. R. Gutzmer: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Johnson&Johnson; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck-Serono; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-MyersSquibb; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Almirall-Hermal; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SUN; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre-Fabre; Honoraria (self), Advisory / Consultancy: LEO; Honoraria (self), Advisory / Consultancy: 4SC; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: Takeda. J.C. Becker: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy: CureVac; Honoraria (self), Advisory / Consultancy: eTheRNA; Honoraria (self), Advisory / Consultancy: Lytix; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Rigontec; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: 4SC; Research grant / Funding (institution): Alcedis; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: Incyt. F. Funkner: Full / Part-time employment: CureVac AG. R. Heidenreich: Full / Part-time employment: CureVac AG. S. Kays: Full / Part-time employment: CureVac AG. U. Klinkhardt: Full / Part-time employment, Former: CureVac; Full / Part-time employment: Boehringer Ingelheim. U.S. Gnad-Vogt: Full / Part-time employment, Officer / Board of Directors: CureVac AG. B. Scheel: Full / Part-time employment: CureVac AG. O. Schönborn-Kellenberger: Full / Part-time employment, consultant to CureVac AG: Cogitars GmbH. T. Seibel: Full / Part-time employment: CureVac AG. All other authors have declared no conflicts of interest.