The past year has brought about several key catalysts propelling precision oncology forward, driven by key drug approvals and an evolving reimbursement landscape for next-generation sequencing. The first tissue-agnostic drug approval, pembrolizumab for patients with microsatellite instability-high or mismatch repair deficient solid tumors, marked a paradigm shift in cancer.
Also in 2017, two drugs (larotrectinib and entrectinib) were given Orphan Drug designation for treatment of NTRK fusion-positive solid tumors. An important story on the diagnostic side is recent FDA approval, and parallel national coverage determination from CMS, of FoundationOne CDx for solid tumors.
Despite these advances, most advanced cancer patients do not have access to comprehensive tumor molecular profiling and precision medicine clinical trials. At the same time, precision therapy trial enrollment is slow and inefficient, resulting in delays bringing new medicines to market.
Health systems need a cost-effective, system-wide solution for precision oncology, one that integrates cutting-edge molecular profiling and precision therapy trials with routine care so that all advanced cancer patients have the opportunity to benefit. Biopharmaceutical companies need a mechanism to rapidly and predictably enroll registration-enabling precision therapy trials.
The Strata Precision Oncology Network is a collaboration of leading health systems that believe in deploying a clinical-research driven model for precision medicine that enables continuous learning to drive research and clinical care. Network members are committed to standardizing tumor molecular profiling and precision therapy trials, providing a much-needed platform to accelerate drug approvals and catalyze new clinical research opportunities.
Members work together to develop best practices, accelerate approval of precision therapies, and share data across 13 institutions, including the following: Aurora Health Care, Gundersen Health System, Helen F. Graham Cancer Center & Research Institute at Christiana Care, Kaiser Permanente Northern California, Colorado and Mid-Atlantic, Kettering Health Network, Metro Minnesota Community Oncology Research Consortium, Ochsner Health System, UAB Comprehensive Cancer Center, UNC Lineberger Comprehensive Cancer Center, University of Texas Health Sciences at Houston, and University of Wisconsin Carbone Cancer Center.
Collectively, the health care providers in the network see more than 90,000 new cancer cases per year across more than 60 hospitals.
Delivering Cancer Care System-Wide
Establishing the infrastructure required for a cutting-edge precision cancer medicine program is a challenge for any health system. Major obstacles include ensuring broad patient access to tumor molecular profiling and precision therapies, as well as facilitating an optimized approach for precision medicine research and clinical trials.
Members of the network implement a comprehensive, streamlined program that features tumor molecular profiling for all advanced cancer patients, robust software and data tools, and matching to a portfolio of pharma-sponsored precision therapy trials.
The Strata Trial serves as the foundation of this approach by providing a standardized genomic testing protocol to deliver precision oncology system-wide. This observational study provides comprehensive tumor molecular profiling for 100,000 advanced cancer patients at no cost and proactive enrollment support for a portfolio of pharma-sponsored precision therapy trials. The study also serves as a mechanism to capture the impact of genomic testing on clinical trial enrollment and other clinical care decisions.
StrataNGS, a targeted assay that sequences DNA and RNA in archival or fresh biopsy tissue, is available at no cost to all advanced cancer patients at member institutions. The test is focused on actionable genomic alterations, covering all FDA-approved markers, those referenced in clinical guidelines, and markers with compelling evidence for investigational medicines. All profiling is performed in a high-throughput Clinical Laboratory Improvement Amendment-certified laboratory so that results can be entered into patient medical records and used to guide treatment decisions.
Data and software tools integrate EMR-based clinical data with molecular profiling data to ensure patients are tested, considered for precision trial enrollment, and tracked post-enrollment.
A portfolio of pharma-sponsored therapeutic protocols aligned to distinct biomarkers is available at the primary cancer center in each health system, thereby increasing trial accrual and maximizing opportunity for patient benefit. The portfolio is comprised of studies that are through proof-of-concept and have the potential for accelerated approval.
Patient & Clinician Benefits
Previous efforts to evaluate the feasibility of routine tumor profiling have resulted in low rates of enrollment into biomarker-guided clinical trials. Key challenges include ineligibility resulting from clinical deterioration, insufficient infrastructure to facilitate timely patient matching, and local availability of relevant trials (J Natl Cancer Inst 2016;108(3):djv332).
To address these challenges, network members implement a streamlined clinical workflow centered on a systematic, rather than individual physician-led approach to deliver routine precision medicine.
Software is used to characterize and prioritize the advanced cancer population at each institution for testing and trial matching, ensuring that every patient has the opportunity to benefit. Tumor molecular profiling through the targeted assay is available at the time of diagnosis of advanced disease, even while on standard therapy, so that eligibility markers for potential protocols can be identified in advance should a patient progress and become eligible for a study. StrataNGS features industry-leading performance on small tissue samples, with success rates of 96 percent and 93 percent on samples <25mm2 and <5mm2, respectively, ensuring most cancer patients can be tested. Test results are turned around in an average of 5 business days or less from receipt of specimen. Proactive trial matching connects patients with actionable alterations to a portfolio of locally available precision therapy trials.
Rapid progress in precision oncology research and therapeutic development demands a streamlined platform for collaboration between health systems and biopharmaceutical companies. This requires a large network of trial-ready health systems with fully pre-screened advanced cancer populations.
By deploying system-wide tumor profiling and an optimized clinical trial infrastructure, the network provides an efficient and accelerated path to new and expanded drug approvals for industry sponsors, featuring rapid trial activation and accrual across a fully functional network of sites. A clinical advisory board comprised of oncologists from network members guides selection of the most promising investigational precision therapies for inclusion a pharma trial portfolio.
A research database of aggregate de-identified clinical and genomic data allows researchers to discover patterns and design previously impractical precision medicine studies. This next-generation clinical-genomic database of potential trial candidates, potentially eligible for immediate enrollment, provides an unprecedented ability to learn from real-world data and rapidly translate insights to active prospective studies. Investigators are currently contemplating multisite investigator-initiated studies leveraging genetically characterized patient cohorts across the network.
Started in 2017, the network is now beginning to bear fruit. Over the next year, plans are to select new members and continue to develop capabilities that support the goal to successfully deliver on the promise of precision medicine. Researchers believe the transcriptome is the next frontier in precision cancer medicine, so one area of focus will be validation of emerging immuno-oncology biomarkers, such as PD-L1, CD8, CD4, and interferon gamma through RNA sequencing.
The addition of new members will further empower the ability to rapidly initiate and complete biomarker-driven trials that result in the timely approval of precision therapies. A growing research database will provide tremendous opportunities for discovery and facilitate identification of unmet needs for novel investigational trials. We believe the network, at scale, will be the most effective mechanism for biopharma and investigators to design and conduct potentially transformative precision medicine studies.
MARC R. MATRANA, MD, MSC, FACP, is Senior Medical Oncologist at the Gayle and Tom Benson Cancer Center; Medical Director of the Precision Cancer Therapies (Phase I) Research Program; Head of the Burns Society at Ochsner/UQ Clinical School; and Associate Director of Clinical Cancer Research at Ochsner Cancer Institute; as well as Senior Lecturer and Key Faculty at the University of Queensland School of Medicine, Brisbane.