A personal neoantigen vaccine, NEO-PV-01, with anti-PD1 induces broad de novo anti-tumor immunity in patients with metastatic melanoma, NSCLC, and bladder cancer (2018)

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. 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.