Abstract 1028P
Background
GEN-009-101 is an ongoing phase I/IIa study of a personalized neoantigen vaccine containing targets selected by ATLAS™, a bioassay using ex vivo screening of autologous T cells to identify stimulatory peptides and “Inhibigens™”, peptides that suppress immunity and could accelerate tumor progression. Previous data showed 99% of selected peptides generated immune responses.
Methods
After next-generation tumor sequencing and ATLAS testing, GEN-009 is formulated with up to 20 stimulatory peptides and poly-ICLC as adjuvant. Eligible patients with advanced cancer received standard-of-care (SOC) PD-1 CPI +/- chemotherapy during vaccine manufacturing and then received 5 vaccine doses over 6 months along with continuation of PD-1 CPI. Patients who progressed prior to vaccination were allowed to receive alternate therapy followed by GEN-009 in combination with an appropriate salvage regimen. The contributions from GEN-009 are to be assessed using each patient as their own control based upon change in tumor volume pre- versus post-vaccination.
Results
Between 4 and 99 neoantigens were identified in 18 patients with assorted histologies. To date 8 patients were vaccinated with GEN-009: 6 in conjunction with SOC PD-1 CPI and 2 with refractory disease received a salvage regimen. 24 vaccine doses have been given. AEs related to GEN-009 include grade 1 injection site reactions in 4 patients, and no DLTs. The ATLAS profile of stimulatory and inhibitory peptides evolved during PD-1 therapy to reflect a greater number of stimulatory targets and fewer inhibigens, suggesting a novel mechanism for CPI. Fluorospot results showed 69% of peptides generated a CD8 response, 85% a CD4 response and that 38% of the peptides did both. Up to 18 enrolled patients will provide insight into the treatment effects.
Conclusions
Vaccination with GEN-009 in combination with PD-1 based therapy for patients with advanced cancer is feasible with little additive toxicity to date. Preliminary data suggests an expansion of stimulatory targets with epitope spreading in the presence of CPI. While early data are promising, the antitumor effect of GEN-009 will need to be evaluated with greater patient numbers.
Clinical trial identification
NCT03633110.
Editorial acknowledgement
Legal entity responsible for the study
Genocea Biosciences.
Funding
Genocea Biosciences.
Disclosure
M. Gillison: Research grant/Funding (institution): Genocea; Research grant/Funding (institution): NIH; Research grant/Funding (institution): Merck; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Shattuck Labs; Research grant/Funding (institution): BioMimetix; Research grant/Funding (institution): NewLink; Research grant/Funding (institution): Cellgene; Research grant/Funding (institution): Rakuten. M.M. Awad: Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Lilly; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Genentech; Advisory/Consultancy: Merck; Advisory/Consultancy: Achilles; Advisory/Consultancy: AbbVie. P. Twardowski: Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Clovis. R.B. Cohen: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Heat Biologics; Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy, Travel/Accommodation/Expenses: Alkermes; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Kyntherapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Innate Pharma; Advisory/Consultancy: Cantargia AB; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genocea; Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Xencor. A. Sukari: Shareholder/Stockholder/Stock options: Immunomedics; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Eisai; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Merck. M. Johnson: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AbbVie; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): Apexigen; Research grant/Funding (institution): Array BioPharma; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Atreca; Research grant/Funding (institution): BeiGene; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim; Research grant/Funding (institution): Checkpoint Therapeutics; Research grant/Funding (institution): Corvus Pharmaceuticals; Research grant/Funding (institution): CytomX; Research grant/Funding (institution), Travel/Accommodation/Expenses: Daiichi Sankyo; Research grant/Funding (institution): Dynavax; Research grant/Funding (institution), Travel/Accommodation/Expenses: Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Research grant/Funding (institution): Genmab; Research grant/Funding (institution): Genocea Biosciences; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Gritstone Oncology; Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Hengrui Therapeutics; Research grant/Funding (institution): Immunocore; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Incyte; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Research grant/Funding (institution): Jounce Therapeutics; Research grant/Funding (institution): Kadmon Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Loxo Oncology; Research grant/Funding (institution): Lycera; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Advisory/Consultancy, Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Neovia Oncology; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution): OncoMed Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Regeneron Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Sanofi; Research grant/Funding (institution): Seven and Eight Biopharmaceuticals; Research grant/Funding (institution): Shattuck Labs; Research grant/Funding (institution): Stem CentRx; Research grant/Funding (institution): Syndax Pharmaceuticals; Research grant/Funding (institution): Takeda Pharmaceuticals; Research grant/Funding (institution): Tarveda; Research grant/Funding (institution): University of Michigan; Research grant/Funding (institution): WindMIL; Research grant/Funding (institution): TCR2 Therapeutics; Research grant/Funding (institution): Arcus Biosciences; Advisory/Consultancy, Research grant/Funding (institution): Ribon Therapeutics; Research grant/Funding (institution): Amgen; Travel/Accommodation/Expenses, Spouse/Financial dependant: Astellas; Spouse/Financial dependant: Otsuka Pharmaceuticals; Advisory/Consultancy: Achilles Therapeutics; Advisory/Consultancy: Calithera Biosciences; Advisory/Consultancy: Lilly; Advisory/Consultancy: Association of Community Cancer Centers; Travel/Accommodation/Expenses: Clovis; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: Exelixis; Travel/Accommodation/Expenses: Sysmex Inostics; Travel/Accommodation/Expenses: Vapotherm. A. DeCillis: Advisory/Consultancy, Full/Part-time employment: DeCillis Consulting; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Licensing/Royalties: Exelixis; Advisory/Consultancy: DSI; Advisory/Consultancy: Pyramid; Advisory/Consultancy: Cybrexa; Advisory/Consultancy: Codiak; Advisory/Consultancy: CytomX; Advisory/Consultancy: Monopteros; Advisory/Consultancy: Evelo. R. Hernandez, J. Price, L. Dowal, M. Shainheit, P. Lapham, M. Jain: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genocea. D.B. DeOliveira: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genocea; Shareholder/Stockholder/Stock options: Ipsen. N. Singh: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Genocea; Shareholder/Stockholder/Stock options, Licensing/Royalties, Patentholder: Momenta; Shareholder/Stockholder/Stock options: Amgen. J.B. Flechtner, T. Davis: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Genocea. All other authors have declared no conflicts of interest.