In a phase 1 clinical trial, Sellars et al. evaluated the adjuvant use of personalized cancer vaccines in combination with nivolumab in patients with high-grade ovarian cancer treated with standard-of-care platinum-based chemotherapy. Treatment was feasible and well tolerated, with evidence of vaccine-induced T cell responses and antitumor immunity. Immune escape through several mechanisms was also observed.
ABSTRACT: Personalized neoantigen-targeting cancer vaccines in the adjuvant setting are of increasing interest across malignancies. Here we report the results of a phase 1 clinical trial testing the feasibility and safety of personalized neoantigen-targeting cancer vaccines for high-grade epithelial ovarian cancer. 'NeoVax' consisted of pools of synthetic long peptides targeting patient-specific neoantigens admixed with the immunostimulant poly-ICLC, was combined with delayed administration of anti-PD-1 antibody, and was tested in ten patients (one newly diagnosed patient (Cohort A) and nine patients at first recurrence (Cohort B)) with platinum-sensitive ovarian cancer following standard-of-care platinum doublet chemotherapy. Nine of 12 evaluable Cohort B patients were vaccinated (75%, 90% CI 47-93%) and 1 of 9 Cohort A patients (11%, 90% CI 0.6-43%). No unexpected safety signals were encountered and no patients discontinued treatment due to toxicity. Across patients, >70% selected targets remained detectable by noninvasive cell-free DNA analysis despite a median of 6.5 months from the time of diagnostic biopsy to vaccine administration, during which, patients received standard-of-care chemotherapy. Biomarker analysis was suggestive of biologic activity of the vaccine in six of ten patients and this was associated with broader tumor and vaccine-specific immune responses in blood and tumor following vaccination. Resistant tumor clones reflected diverse mechanisms affecting antigen presentation, indicative of immune-selective pressure exerted by vaccination. Overall, the interplay between the repertoire of antigens presented by the tumor and the breadth of induced immunity seemed to dictate clinical efficacy following vaccination. ClinicalTrials.gov identifier: NCT04024878 .
Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Department of Medical Oncology, Dana-Farber Cancer I
Author Info: (1) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (2) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (3) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. (4) Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (5) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (6) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. (7) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. (8) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (9) Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (10) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. (11) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (12) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (13) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (14) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (15) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (16) Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (17) Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (18) Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (19) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (20) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Centre for Immuno-Oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK. (21) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (22) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (23) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (24) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. (25) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (26) Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA. (27) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (28) Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. (29) Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. (30) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. (31) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (32) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (33) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (34) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (35) Broad Institute of MIT and Harvard, Cambridge, MA, USA. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA. Department of Pathology, Harvard Medical School, Boston, MA, USA. (36) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. (37) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. (38) Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, USA. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. (39) Broad Institute of MIT and Harvard, Cambridge, MA, USA. (40) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Harvard Medical School, Boston, MA, USA. Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA, USA. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. Department of Medical Education and Biomedical Sciences, Methodist University CFVH School of Medicine, Fayetteville, NC, USA. (41) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Panogiotis_Konstantinopoulos@dfci.harvard.edu. Harvard Medical School, Boston, MA, USA. Panogiotis_Konstantinopoulos@dfci.harvard.edu. Mellen and Eisenson Family Center for BRCA and Related Genes, Dana-Farber Cancer Institute, Boston, MA, USA. Panogiotis_Konstantinopoulos@dfci.harvard.edu. (42) Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Catherine_Wu@dfci.harvard.edu. Harvard Medical School, Boston, MA, USA. Catherine_Wu@dfci.harvard.edu. Broad Institute of MIT and Harvard, Cambridge, MA, USA. Catherine_Wu@dfci.harvard.edu. Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Catherine_Wu@dfci.harvard.edu.
