Cancer cells harbor DNA mutations that encode altered amino acid sequences known as neoantigens. Absent from normal tissues and highly specific for tumors, neoantigens bypass central tolerance and have been established as critical targets for tumor directed T cell responses. Tumor mutational burden and neoantigen load have been associated with anti-tumor activity of immune checkpoint inhibitors. Vaccines targeting neoantigens have the potential to induce de novo and expand existing tumor directed T cell responses. NEO-PV-01 is a personalized neoantigen long peptide vaccine designed specifically for the molecular profile of an individual patient’s tumor.
NT-001 is a single-arm, phase IB study evaluating the safety of administering NEO-PV-01 + adjuvant (Poly-ICLC) with the PD-1 directed antibody, nivolumab, in patients with advanced melanoma, smoking-associated non-small cell lung carcinoma, or transitional cell carcinoma of the bladder who have received no more than one prior systemic treatment. NEO-PV-01 is custom designed and generated for each patient by DNA and RNA sequencing of a recently biopsied tumor, HLA typing, selection of neoantigen epitopes, and synthesis of up to 20 peptides (14-35 amino acids in length). Patients receive treatment with nivolumab at a dose of 240 mg IV q2 weeks while their vaccine is produced. These peptides are formulated into four distinct pools, mixed with Poly-ICLC, and administered subcutaneously into up to 4 non-rotating anatomical sites. Beginning at Week 12, patients receive five priming immunizations over a three-week period followed by booster vaccinations at Weeks 19 and 23 while continuing nivolumab. The primary endpoint is safety. Secondary endpoints are ORR, CBR, PFS, and assessment of response conversion between Week 12 and Week 24. Exploratory endpoints include extensive immune monitoring. The study is open as of October 2016 with estimated enrollment of 90 patients.
Clinical trial identification
Legal entity responsible for the study
Neon Therapeutics, Inc.
Neon Therapeutics, Inc.
P.A. Ott: Reports grants and personal fees from Bristol-Myers Squibb, CytomX, Celldex, and Merck, personal fees from Neon Therapeutics, Amgen, Novartis, Pfizer, and Roche/Genentech, and grants from AstraZeneca/MedImmune, outside of the submitted work. G. Ramaswamy: Reports advisory board or consulting work for Merck, Genentech, Baxalta, Roche, Boehringer Ingelheim, Novartis, Ariad, Astellas, Bristol-Myers Squibb, Pfizer, Celgene, AstraZeneca, INC Research, AbbVie, and MSKCC. M. Moles, R. Gaynor, M.J. Goldstein: Employee of Neon Therapeutics, Inc. S. Hu-Lieskovan: Consulting: Amgen, Merck, Novartis, Vaccinex, Emergent BioSolutions. Contracted Research: Pfizer, Plexxikon, Genentech, Neon Therapeutics. Research Support: Bristol-Myers Squibb, Merck. Travel: Amgen, Merck, Novartis, Vaccinex, Emergent BioSolutions, Neon Therapeutics. All other authors have declared no conflicts of interest.