Ontario-wide Cancer TArgeted Nucleic acid Evaluation (OCTANE)

Aim/goals:

1. Develop a province-wide registry of NGS panel-based testing results
2. Expand collaborations for whole genome and NGS panel-based testing in Ontario clinical genetic testing laboratories
3. Develop a province-wide repository of genomically-characterized tumor tissue and blood samples for future research
4. Facilitate targeted therapy and immune therapy clinical trials in Ontario
5. Establish a large province-wide genomically-characterized and clinically-annotated patient base that can be enrolled into specific research initiatives
6. Provide molecular profiling information to treating physicians that may guide future treatment decisions
7. Compare the outcome of patients with genomically-informed treatment matching with patients who do not receive genomically-informed treatment matching
8. Data share with other groups or organizations to enhance big data learning

Summary:

Ontario-wide Cancer TArgeted Nucleic acid Evaluation (OCTANE) is an Ontario-wide alliance supported by the Ontario Institute for Cancer Research (OICR) that provides next generation sequencing (NGS)-based molecular profiling at seven Ontario cancer centres including the Princess Margaret Cancer Centre (PM), London Health Sciences Centre (LHSC), Kingston General Hospital (KGH), The Ottawa Hospital (TOH), the Juravinski Cancer Centre (JCC), Sunnybrook Health Sciences Centre (SHSC), and Mount Sinai Hospital (MSH). The OCTANE infrastructure allows Ontario clinical labs to expand their capacity for clinical molecular testing that will directly benefit patients in Ontario. Patients with advanced solid tumors can have archival tumor tissue genetically tested on NGS technology. Testing results inform the use of approved therapies (if appropriate), facilitate targeted therapy and immune therapy clinical trials in Ontario, and identify patient subsets for additional research studies and/or deeper genomic characterization. All participating patients are asked to provide additional archival tumor, blood samples, and permission for data sharing with other cancer researchers in an effort to establish a province-wide repository of tumor tissue and blood samples for future research, as well as a large database of genomically-characterized and clinically-annotated sequencing results. Linkages to provincial administrative databases (e.g. Cancer Care Ontario New Drug Funding Program, Provincial Cancer Registry, etc.) facilitated through the Institute for Clinical Evaluation sciences provide opportunities to assess the downstream impact of NGS testing subsequent drug treatments and survival.

To date, multiple investigators within the OCTANE network have leveraged the use of banked OCTANE biospecimens in hypothesis-driven research studies of diagnostic utility, clinical impact, or unmet need in cancer care. One such project includes the whole genome and transcriptome sequencing (WGTS) of banked tumor DNA/RNA and germline DNA from 33 OCTANE cases that enabled clinical validation of WGTS in the OICR Genomics laboratory. These OCTANE samples have contributed toward accreditation by the College of American Pathologists and Accreditation Canada to enable WGTS assays. We have now made these data available along with comprehensive clinical data through the MOHCCN and will continue to expand the data set with additional clinically-reported WGTS cases.

A second cohort of OCTANE cases identified as long-term responders to immunotherapy has been selected by MOHCCN for deeper genomic characterization in an effort to understand mechanisms of sensitivity and resistance to immunotherapy—a priority scientific question for MOHCCN. This cohort includes 35 PM patients treated with immune checkpoint inhibitors outside of clinical trials with prolonged clinical benefit (duration of treatment greater than one year), and have available tumor DNA/RNA and germline DNA in the OCTANE biorepository. Samples will undergo WGTS through OICR Genomics and multi-plex immune profiling. Comprehensive clinical data will also be curated for contribution toward MOHCCN Year 1.

Additionally, a third cohort of OCTANE cases was selected for inclusion in MOHCCN Year 2. This cohort consists of 50 OCTANE cases with no actionable alteration found on clinical testing via the Oncomine Comprehensive Assay v3 (OCAv3) or TruSight Oncology 500 (TSO500) panels, and with available tumor DNA/RNA and germline DNA in the OCTANE biorepository. Samples will undergo multi-plex immune profiling as well as WGTS in an effort to find driver mutations. Comprehensive clinical data will also be curated for contribution toward MOHCCN Year 2.