Abstract 4727
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) 200 mg 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 16 pt-specific targets met the qualifying confidence score threshold.
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).Table: 113P
Endpoint | ORR N = 72* | CBR N = 72* | Endpoint | PFS N = 73* | OS N = 73* | ||||
---|---|---|---|---|---|---|---|---|---|
Subgroup | CR/PR N = 15 | SD/PD N = 57 | CR/PR/SD≥6 cycles N = 22 | CR/PR/SD<6 cycles N = 50 | Subgroup | ↑ from baseline N = 33 | ↓ from baseline N = 40 | ↑ from baseline N = 33 | ↓ from baseline N = 40 |
ΔctDNA (% change) | Median = -91.5% Range = -100% to 60% | Median = 40% Range = -98.4% to 2458% | Median = -75% Range = -100% to 96% | Median = 52% Range = -94.6% to 2458% | Results based on ΔctDNA | Median = 7.9m 6m = 51.5% | Median = 2.8m 6m = 10.0% | Median = not reached 6m = 91% 12m = 82% | Median = 9.1m 6m = 73% 12m = 45% |
P-value | P < 0.001 | P < 0.001 | Adjusted HR (95% CI)^ | 0.43 (0.25-0.75) P = 0.003 | 0.35 (0.18–0.67) P = 0.002 |
Adjustment on cohorts;
*2 pts were excluded from ORR/CBR analyses as baseline ctDNA = 0; 1 of these 2 pts (with PR) excluded from PFS/OS analyses as C3 ctDNA = 0
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.
Editorial acknowledgement
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.
Resources from the same session
3489 - Overall Survival (OS) and Metastasis-Free Survival (MFS) in men with Biochemically Relapsed (BCR) Prostate Cancer after radical prostatectomy (RP) managed with deferred Androgen Deprivation Treatment (ADT): A combined Johns Hopkins and CPDR study
Presenter: Catherine Marshall
Session: Poster Display session 3
Resources:
Abstract
4606 - ARCHES – the role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups
Presenter: Arnulf Stenzl
Session: Poster Display session 3
Resources:
Abstract
2975 - Updated survival analyses of a multicentric phase II randomized trial of docetaxel (D) plus enzalutamide (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) (CHEIRON study).
Presenter: Orazio Caffo
Session: Poster Display session 3
Resources:
Abstract
2708 - Real-world analysis of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving vs not receiving chemotherapy in the treatment sequence
Presenter: Alicia Morgans
Session: Poster Display session 3
Resources:
Abstract
2134 - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial
Presenter: Janet Brown
Session: Poster Display session 3
Resources:
Abstract
3504 - Risk of falls and fractures in patients with castration resistant prostate cancer (CRPC) treated with new hormonal agents – a meta-analysis of randomized controlled trials.
Presenter: Rodrigo Coutinho Mariano
Session: Poster Display session 3
Resources:
Abstract
2342 - Pain progression at initiation of chemotherapy in metastatic Castration-Resistant Prostate Cancer (mCRPC) is associated with a poor prognosis: a post-hoc analysis of FIRSTANA
Presenter: Nicolas Delanoy
Session: Poster Display session 3
Resources:
Abstract
5331 - Pain evaluation in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the PARABO observation study
Presenter: Holger Palmedo
Session: Poster Display session 3
Resources:
Abstract
2823 - Time to castration resistant prostate cancer (CRPC) and the risk of developing immune disorders
Presenter: Vincenza Conteduca
Session: Poster Display session 3
Resources:
Abstract
1500 - Retrospective evaluation of neutropenic admission events in metastatic or high-risk hormone-sensitive prostate cancer (HSPC) patients having docetaxel chemotherapy upfront or for castrate-resistant prostate cancer (CRPC) in STAMPEDE
Presenter: Harriet Mintz
Session: Poster Display session 3
Resources:
Abstract