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
4489 - A Window of Opportunity Trial of Atorvastatin Targeting p53 Mutant Malignancies
Presenter: Joaquina Baranda
Session: Poster Display session 3
Resources:
Abstract
1945 - Randomized Phase II Study of Trabectedin/Olaparib Compared to Physician’s Choice in Subjects with Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies.
Presenter: Christoph Heilig
Session: Poster Display session 3
Resources:
Abstract
3021 - Homogenisation of Leftover Surgical Tissue across multiple cancer types: a Feasibility Study (HoLST-F)
Presenter: Lavinia Spain
Session: Poster Display session 3
Resources:
Abstract
2882 - Safety, efficacy, and immune effects of intratumoral tilsotolimod in patients with refractory solid tumors: updated results from ILLUMINATE-101
Presenter: Hani Babiker
Session: Poster Display session 3
Resources:
Abstract
1950 - Phase 1 Dose Escalation of MSC-1, a humanized anti-LIF monoclonal antibody, in patients (pts) with advanced solid tumors: Updated results
Presenter: Erkut Borazanci
Session: Poster Display session 3
Resources:
Abstract
2391 - A phase 1 study of Sym021, an anti-PD-1 antibody (Ab), alone and in combination with Sym022 (anti-LAG-3) or Sym023 (anti-TIM-3)
Presenter: Anna Spreafico
Session: Poster Display session 3
Resources:
Abstract
5692 - FPA150 (B7-H4 antibody) Phase 1 Update in Advanced Solid Tumors: Monotherapy and in Combination with Pembrolizumab
Presenter: Zev Wainberg
Session: Poster Display session 3
Resources:
Abstract
2416 - MG1124, a novel CEACAM1-targeted monoclonal antibody, has therapeutic potential as a combination partner of PD-1 inhibitors in NSCLC patients
Presenter: Eun Hee Lee
Session: Poster Display session 3
Resources:
Abstract
2661 - Tumor stroma targeting and modulation by OMTX705 ADC, a novel and potent immunotherapeutic treatment of solid tumors.
Presenter: Myriam Fabre
Session: Poster Display session 3
Resources:
Abstract
3681 - Durvalumab + monalizumab, mFOLFOX6, and bevacizumab in patients (pts) with metastatic microsatellite-stable colorectal cancer (MSS-CRC)
Presenter: May Cho
Session: Poster Display session 3
Resources:
Abstract