Abstract 3041
Background
High tissue-tumor mutation burden (tTMB) is a predictor of response to immunotherapy (IO). Tissue availability and tumor heterogeneity are barriers to tTMB use in clinical practice. Plasma-based blood TMB (bTMB) is a convenient alternative that strongly correlates with tTMB in non-small cell lung cancer. Whether this correlation holds true in other cancers is unknown. Here, we examined the correlation between bTMB and tTMB as well as the clinical utility of TMB as a predictive marker of response in a heterogeneous Phase I IO cohort.
Methods
Advanced cancer patients (pts) treated with mono- or combination IO therapy at the Princess Margaret phase I unit were enrolled. Pre-treatment plasma ctDNA and matched normal blood controls were collected via an institutional liquid biopsy program (LIBERATE, NCT03702309). Available archival tissue FFPE samples were analyzed. The GeneseeqPrime 425 gene panel was used to sequence both ctDNA and FFPE samples.
Results
From December 2017 to July 2018, 39 pts with 19 tumor types were accrued from 25 different trials, 87% of which involved a PD-1/PD-L1 inhibitor. The median age was 59y (21 – 77) and 52% were female. The most frequent cancers were colorectal, head and neck and breast, each with 5 cases. Thirty-one patients (79%) had detectable mutations in plasma ctDNA. The median bTMB was 5 (1 - 53) mut/Mb. Twenty-one pts had available FFPE samples. Of those, mutations were detected in 20 (95%) samples. The median tTMB was 6 (2 - 124) mut/Mb. Among the 16 pts with detectable mutations in both FFPE and plasma samples, a significant correlation between bTMB and tTMB was observed (r = +0.67; p < 0.01). For survival analysis, 1 pt was excluded due to screen failure. The median PFS and OS for the entire cohort were 1.84m and 8.47m, respectively, with 3 (8%) partial response (PR), 11 (29%) stable disease (SD), and 24 (63%) progressive disease (PD). There was no association between bTMB or tTMB with survival; however, 2 of 3 PRs (anal and MSI-H endometrial cancer) exhibited a high bTMB of 53 and 46, respectively.
Conclusions
In a typical heterogeneous phase I IO cohort, bTMB was correlated with tTMB. In this small series, neither bTMB nor tTMB were associated with survival. However, 2/3 PRs had high bTMB. Further studies in larger cohorts are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Lillian Siu.
Funding
Princess Margaret Cancer Centre; BMO Chair in Precision Genomics; Geneseeq Technology Inc.
Disclosure
A. Wang: Full / Part-time employment: Geneseeq Technology Inc. J. Huang: Full / Part-time employment: Geneseeq Technology Inc. A. Spreafico: Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Oncorus; Travel / Accommodation / Expenses: Idera; Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (self): Symphogen; Research grant / Funding (self): AstraZeneca/MedImmune; Research grant / Funding (self): Surface Oncology; Research grant / Funding (self): Jansseen Oncology; Research grant / Funding (self): Northern Biologics. A.R. Hansen: Advisory / Consultancy: Genentech/Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): GlaxoSmithKline; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Boston Biomedical; Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca/MedImmune; Honoraria (self): Pfizer; Research grant / Funding (institution): Karyopharm Therapeutics. A.A. Razak: Advisory / Consultancy, Research grant / Funding (self): Lilly; Advisory / Consultancy, Research grant / Funding (self): Merck; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): CASI Pharmaceuticals; Research grant / Funding (self): Novartis; Research grant / Funding (self): Deciphera; Research grant / Funding (self): Karyopharm Therapeutics; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche/Genentech; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Amgen; Research grant / Funding (self): GlaxoSmithKline; Research grant / Funding (self): Blueprint Medicines; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Adaptimmune. P. Bedard: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Servir; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): SignalChem; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Nektar; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Immunomedics; Research grant / Funding (institution): Lilly. H. Bao: Full / Part-time employment: Geneseeq Technology Inc. X. Wu: Leadership role, Full / Part-time employment: Geneseeq Technology Inc. T.J. Pugh: Advisory / Consultancy: DynaCare; Licensing / Royalties: Hybrid-capture sequencing for determining immune cell clonality; Licensing / Royalties: Combined hybrid-capture DNA sequencing for disease detection; Honoraria (self): Merck; Honoraria (self): Prosigna; Honoraria (self): Chrysalis Biomedical Advisors; Research grant / Funding (institution): Boehringer Ingelheim. L.L. Siu: Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca/MedImmune; Advisory / Consultancy: MorphoSys; Advisory / Consultancy, Research grant / Funding (institution): Symphony Evolution; Advisory / Consultancy, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Loxo; Shareholder / Stockholder / Stock options, Spouse / Financial dependant, Immediate Family Member - Leadership and Stock/Owenership: Angios; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Astellas Pharma. All other authors have declared no conflicts of interest.
Resources from the same session
2743 - The Impact of Targeted Therapies and Immunotherapy in Melanoma Brain Metastases: a Systematic Review and Meta-Analysis
Presenter: Mario Mandala
Session: Poster Display session 3
Resources:
Abstract
5479 - Intracranial Anti-Tumor Activity in Melanoma Brain Metastases with Encorafenib Plus Binimetinib: A Multicenter, Retrospective Analysis
Presenter: Jose Lutzky
Session: Poster Display session 3
Resources:
Abstract
3560 - Outcomes of Patients with Melanoma Brain Metastases (MBM) Treated with Standard of Care Therapy After Being Excluded from MBM-Specific Clinical Trials
Presenter: Kourtney Holbrook
Session: Poster Display session 3
Resources:
Abstract
3175 - The analysis of current treatment outcomes in melanoma patients with brain metastases
Presenter: Joanna Placzke
Session: Poster Display session 3
Resources:
Abstract
4550 - A multivariate model to define prognostic groups among patients with melanoma brain metastases: a 10-year retrospective cohort study
Presenter: Giacomo Pelizzari
Session: Poster Display session 3
Resources:
Abstract
4191 - The immune landscape of melanoma significantly influences survival in patients with highly mutated tumors.
Presenter: Robert Ferguson
Session: Poster Display session 3
Resources:
Abstract
1625 - Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
Presenter: Kenji Yokota
Session: Poster Display session 3
Resources:
Abstract
5346 - Evaluating polygenic risk score prediction model for melanoma prognosis
Presenter: Miriam Potrony
Session: Poster Display session 3
Resources:
Abstract
5477 - Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Presenter: Maria Grazia Vitale
Session: Poster Display session 3
Resources:
Abstract
3469 - Ancillary evaluation of systemic immune antitumor response (SIAR) and tumor growth rate (TGR) of patients (pts) with metastatic melanoma (MM) treated with radiotherapy (RT) combined with ipilimumab (ipi) in the phase 1 study Mel-Ipi-Rx.
Presenter: Celine Boutros
Session: Poster Display session 3
Resources:
Abstract