A Personal Neoantigen Vaccine, NEO-PV-01, with anti-PD1 Induces Broad De Novo Anti-Tumor Immunity in Patients with Metastatic Melanoma, NSCLC, and...

Date 22 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Immunotherapy of Cancer
Topics Melanoma
Urothelial Cancers
Clinical Research
Tumour Immunology
Immunotherapy
Presenter Patrick Ott
Citation Annals of Oncology (2018) 29 (suppl_8): viii400-viii441. 10.1093/annonc/mdy288
Authors P.A. Ott1, R. Govindan2, A. Naing3, T.W. Friedlander4, K. Margolin5, J.J. Lin6, N. Bhardwaj7, M.D. Hellman8, L. Srinivasan9, J. Greshock9, M. Moles9, R.B. Gaynor10, M.J. Goldstein10, S. Hu-Lieskovan11
  • 1Medical Oncology, Dana Farber Cancer Institute, 02215 - Boston/US
  • 2Internal Medicine, Division Of Oncology, Washington University in St. Louis, St. Louis/US
  • 3Division Of Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 4Department Of Medicine, UCSF, San Francisco/US
  • 5Medical Oncology, City of Hope National Medical Center, Duarte/US
  • 6Department Of Medicine, Massachusetts General Hospital, Boston/US
  • 7Department Of Medicine, Mt. Sinai School of Medicine, New York/US
  • 8Department Of Medicine, Memorial Sloan Kettering Cancer Center, New York/US
  • 9Research & Development, Neon Therapeutics, Inc., Cambridge/US
  • 10Research & Development, Neon Therapeutics, Inc., 02139 - Cambridge/US
  • 11Medical Oncology, UCLA/JCCC, Los Angeles/US

Abstract

Background

Neoantigens arise from DNA mutations in cancer cells and are important targets for T cells. Adjuvant therapy with a personal neoantigen vaccine induced T cell responses in melanoma (mel) patients and suggested synergy with anti-PD1 mAbs (Ott et al, Nature 2017). NEO-PV-01 is a personal neoantigen vaccine of up to 20 peptides (14-35 amino acids) designed based on bioinformatic analysis of a patient’s neoantigen and HLA profile. We report clinical and immune data of NEO-PV-01 in combination with nivolumab (nivo) in metastatic cancer.

Methods

NT-001 is a single-arm, phase 1b study of NEO-PV-01 with nivo in advanced mel, NSCLC, or bladder cancer. Patients begin nivo at Week 0 and at Week 12 receive NEO-PV-01 vaccine plus adjuvant Poly-ICLC in a prime-boost format. The primary endpoint is safety; secondary endpoints include overall response rate (ORR) and response conversion rate. Comprehensive immune assessments are performed throughout with biopsies at Weeks 0, 12 and 24.

Results

31 patients received at least one vaccination by the data cut and 19 had completed the full vaccine course. Vaccine-related AEs were mild (e.g., grade 1/2 injection site reactions and flu-like symptoms), with no vaccine-related SAEs. For post vaccination patients, the ORR was 52.6% (n = 10), with 2 mel and 1 NSCLC patient having response conversions. 13 patients remain on treatment (11 mel, 1 NSCLC, 1 bladder). Immune analysis was completed on 9 patients (including all 3 tumor types). Ex vivo neoantigen-specific CD4 and CD8 T cell responses against >60% of vaccine peptides were polyfunctional and of a memory phenotype. Epitope spreading post-vaccination (T cell responses to neoantigens not in the vaccine but in the patient’s tumor) was observed in 4 of 6 patients analyzed. In a subset of patients, pathologic review of pre- vs post-vaccine biopsies showed decreased tumor cellularity following vaccination.

Conclusions

Treatment with NEO-PV-01 and nivo has minimal toxicity and promising clinical activity. NEO-PV-01 is effective in inducing broad de novo neoantigen-specific immune responses in patients with metastatic cancers.

Clinical trial identification

NCT02897765.

Legal entity responsible for the study

Neon Therapeutics, Inc.

Funding

Neon Therapeutics, Inc.

Editorial Acknowledgement

Disclosure

P.A. Ott: Consulting: Neon, BMS, Merck, Novartis, Pfizer, Roche/Genentech, Celldex, CytomX. R. Govindan: Consulting and honorarium: Genentech; Advisory board: Genentech, Pfizer, Nektar, Inivata, NeoHealth, BMS. A. Naing: Research funding: NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor, Amplimmune, Armo Biosciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Baxter (spouse). T.W. Friedlander: Advisory board: Genetech, Pfizer, AstraZeneca; Research funding: Novartis, Incyte, Janssen. J.J. Lin: Honorarium: Chugai, Boehringer-Ingelheim. N. Bhardwaj: Advisory board: Neon Therapeutics, Inc. M.D. Hellman: Advisory board: Genentech/Roche, BMS, AstraZeneca, Merck, Janssen, Norvartis, Mirati, Shattuck Labs; Research support: BMS. L. Srinivasan, J. Greshock, M. Moles, R.B. Gaynor, M.J. Goldstein: Employee: Neon Therapeutics, Inc. S. Hu-Lieskovan: Consulting: Amgen, Merck, Genmab, Xencor; Research support: BMS, Merck, Vaccinex. All other authors have declared no conflicts of interest.