Abstract 3021
Background
Intratumour heterogeneity is recognised across different tumour types and has implications for therapeutic resistance. At present, clinical practice often relies upon molecular information derived from a single biopsy of a primary or metastatic tumour. This information guides treatment choice but may not be representative of the diversity of the tumour. It is currently difficult to evaluate how effectively a single region guides treatment decisions because the formalin-fixed residual surgical sample that is not paraffin embedded for diagnostic purposes is typically thrown away. Retention and homogenisation – ‘blending’- of this residual formalin-fixed leftover tumour tissue creates a more representative sample for analysis. DNA may be extracted from this sample for sequencing. Pilot data in kidney cancer has demonstrated the potential of this methodology for robust mutational calling, accurate determination of cancer cell fraction and the ability to discern clonal from subclonal variants. Such information may be clinically relevant; for example, discerning resistant subclones prior to treatment, or identifying clonal neoantigens worth targeting with immunotherapy.
Trial design
In order to establish the feasibility of homogenization as a potential companion diagnostic tool, our study aims to 1) identify the proportion of primary tumour cases that have left over tissue amenable to homogenization across multiple tumour types and 2) pilot homogenization across multiple tumour types. The molecular profile of the homogenate will be compared to that obtained from the diagnostic specimen using next generation sequencing techniques. This is a prospective non-interventional study (NCT03832062). Patients undergoing surgical intervention at The Royal Marsden Hospital (NHS Foundation Trust) with leftover tumour tissue from primary breast, colorectal, gastric, pancreatic, ovarian, renal cancer and sarcoma surgeries, as well as melanoma lymph node dissections will be included in the feasibility assessment. We plan to homogenise 500 cases across different tumour types. The study opened in September 2018 and is expected to run for 2 years.
Clinical trial identification
NCT03832062; Release date: February 2019.
Editorial acknowledgement
Legal entity responsible for the study
Royal Marsden NHS Foundation Trust.
Funding
Ventana Medical Systems (a subsidiary of Roche).
Disclosure
L. Gallegos: Full / Part-time employment: Roche. S. Hill: Full / Part-time employment: Roche. A. Barhoumi: Full / Part-time employment: Roche. S. Stanislaw: Full / Part-time employment: Roche. M. Mendoza: Full / Part-time employment: Roche. J.M.G. Larkin: Research grant / Funding (institution): Roche; Advisory / Consultancy: Roche. N. Alexander: Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Roche. S. Turajlic: Research grant / Funding (institution): Ventana Medical Systems (subsidiary of Roche). All other authors have declared no conflicts of interest.
Resources from the same session
5760 - Landscape of PD-L1 expression status in Chinese solid tumor patients.
Presenter: Yi Zhong
Session: Poster Display session 3
Resources:
Abstract
3733 - Anti-cancer and immunomodulatory effects of cobimetinib in triple negative breast cancer
Presenter: Chun-Yu Liu
Session: Poster Display session 3
Resources:
Abstract
4426 - Differential expression of immunoregulatory molecules and highly-associated cancer genes may provide novel insights into strategic trial design for therapeutics
Presenter: Jacob Adashek
Session: Poster Display session 3
Resources:
Abstract
2752 - Insights into the Tumor Immune Microenvironment using Tissue Phenomics to Drive Cancer Immunotherapy
Presenter: Martin Groher
Session: Poster Display session 3
Resources:
Abstract
5713 - Immune competent somatic mosaic model of colorectal cancer
Presenter: Stefania Napolitano
Session: Poster Display session 3
Resources:
Abstract
1898 - Genomic correlates of response to anti-PDL1 Atezolizumab in non-small-cell lung cancer OAK and POPLAR trials
Presenter: Hari Singhal
Session: Poster Display session 3
Resources:
Abstract
3246 - Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison
Presenter: Yohann Loriot
Session: Poster Display session 3
Resources:
Abstract
3311 - High level of activity of Nivolumab anti-PD-1 immunotherapy and favorable outcome in metastatic/refractory MSI-H non-colorectal cancer: Results of the MSI cohort from the French AcSé program
Presenter: Christophe Tournigand
Session: Poster Display session 3
Resources:
Abstract
2314 - TP53 and ATM Co-mutation Predicts Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer
Presenter: Yu Chen
Session: Poster Display session 3
Resources:
Abstract
4692 - Immune cell biomarkers on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA NSCLC patients
Presenter: Raquel Laza-Briviesca
Session: Poster Display session 3
Resources:
Abstract