Maggie C. Louie, Stephanie Lheureux, Zhihui (Amy) Liu, Cindy Yang, W. Xu, Alexey Aleshin, Scott Dashner, Scott V. Bratman, Trevor J. Pugh, Aaron R. Hansen, P. Bedard, Pamela S. Ohashi, L.L. Siu, Albiruni Ryan Abdul Razak, H.-T. Wu, Himanshu Sethi, Marco A. J. Iafolla, Svetlana Shchegrova, Anna Spreafico, and Dax Torti
Background Limited data exist in the clonal dynamics of serial ctDNA as a predictive biomarker in advanced solid tumor pts receiving immune checkpoint blockade. Methods Pts with mixed solid tumors received single agent P (anti-PD-1) 200mg IV Q3wks in the investigator-initiated phase II INSPIRE trial (NCT02644369). ctDNA was assayed at baseline (B) and start of cycle 3 (C3) using a pt-specific amplicon-based NGS assay (Signatera™). Samples were considered ctDNA positive if≥2 of 16pt-specific targets met the qualifying confidence score threshold.Table: 113PTable: 113PEndpointORR N=72*CBR N=72*EndpointPFS N=73*OS N=73*SubgroupCR/PR N=15SD/PD N=57CR/PR/SD≥6 cycles N=22CR/PR/SD Results Of 94 pts are presented. Demographics: male 38%; median age=55 yrs (range 21–81); triple negative breast (19%), ovarian (19%) and head and neck (17%) cancers comprised the major malignancies. Median no. of P cycles=3 (range 1–35); follow up was 14m (range 0.6-35.4); RECIST responses: CR 3.2% (n=3), PR 14% (n=13), CBR (CR+PR+SD>6 cycles) 28% (n=26), RECIST/clinical PD (n=61/18; 65%/19%). Median PFS=2.5m and median OS=14m. In all 94 pts, ctDNAB correlated with PFS (adjusted HR 0.53, 95% CI 0.34-0.84, p=0.01) and OS (adjusted HR 0.47, 95% CI 0.28-0.8, p=0.01). Among 74 pts with both ctDNAB and ctDNAC3, the change (ΔctDNA) correlated with clinical efficacy parameters (Table). Conclusions Strong correlations exist between both ctDNAB and ΔctDNA with clinical outcome, suggesting both prognostic and predictive values in pts with mixed solid tumors. Clinical trial identification NCT02644369, December 31, 2015. Legal entity responsible for the study University Health Network, Toronto. Funding Merck, Netera, Terry Fox Research Institute, Princess Margaret Cancer Foundation. Disclosure S. Dashner: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. A.R. Hansen: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Boehringer-Ingelheim; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Karyopharm. P. Bedard: Honoraria (institution), Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Nektar Therapeutics; Research grant / Funding (institution): Servier; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Oncothyreon. S. Lheureux: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Tesaro. A. Spreafico: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Oncorus; Research grant / Funding (institution): Symphogen; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Surface Oncology; Research grant / Funding (institution): Northern Biologics; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Oncology/Johnson & Johnson; Research grant / Funding (institution): Array Biopharma. A.A. Razak: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): CASI Pharmaceuticals; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Deciphera; Research grant / Funding (institution): Karyopharm Therapeutics; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Boston Biomedical; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): AstraZeneca/Medimmune; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Blueprint Medicines; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Adaptimmune. H. Wu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. S. Shchegrova: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. P.S. Ohashi: Honoraria (self), Advisory / Consultancy: Symphogen Inc; Honoraria (self), Advisory / Consultancy: Providence Therapeutics. M. Louie: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. H. Sethi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. A. Aleshin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Netera. L.L. Siu: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfiser; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/Medimmune; Honoraria (self), Advisory / Consultancy: Morphosys; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Honoraria (self), Advisory / Consultancy: GeneSeeq; Honoraria (self), Advisory / Consultancy: Loxo; Honoraria (self), Advisory / Consultancy: Oncorus; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Symphogen; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boerhinger-Ingelheim; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Karyopharm; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Intensity Therapeutics; Research grant / Funding (institution): Mirati; Research grant / Funding (institution): Shattucks; Spouse / Financial dependant: Agios. S. Bratman: Research grant / Funding (self): Nektar Therapeutics; Licensing / Royalties, Co-inventor of a patent relating to circulating tumor DNA detection technology: Roche Molecular Diagnostics. T.J. Pugh: Honoraria (self): Merck; Honoraria (self): Prosigna; Honoraria (self): Chrysalis Medical Advisors; Advisory / Consultancy: DynaCare; Research grant / Funding (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.