Tumor Mutational Burden (TMB)
Tumor mutational burden (TMB) measures the quantity of mutations found in a tumor. This type of biomarker is currently under study to evaluate whether it may help predict the likelihood a patient with cancer will benefit from immuno-oncology (IO) therapies.
Currently, there is a lack of standardization for TMB calculation and reporting. Different tests may report different measurements, and since there is currently no one way of calculating TMB it is difficult to use as a biomarker. To achieve consistency and accurate reporting across tests, it is imperative to create some sort of standardization to arrive at clinically-meaningful results, which will support informed decision-making for patients.
Friends of Cancer Research (Friends) will convene stakeholders across all health sectors to review the current methods of TMB calculation and reporting and create a consensus solution on how best to standardize them. The group will propose analytical and clinical validation studies to support a standardized method of TMB measurement and reporting, which will help improve patient care through consistent reporting in a clinical setting despite differences in the testing panel used. Ultimately, this project will help ensure consistent identification of patients who are likely to respond to IO therapies.
For more information on this project, Click HERE.
Real-World Evidence (RWE)
Real-world evidence (RWE) is the clinical evidence derived from data on the uses and potential benefits and/or risks of a medical product outside of a traditional clinical trial. This type of data and evidence are being studied to gain an improved understanding as to how they can relate to more traditional clinical endpoints and the long-term benefits of a product. Clinical trials do not necessarily reflect the breadth of data that can be collected in a more diverse real-world setting. There has been a lot of interest in RWE; however, parameters of use and conditions of use have not been well defined. Traditional clinical endpoints may be difficult to obtain and evaluate from real world data. New metrics may be necessary.
There needs to be a standard dataset curation process and validated framework so data collection can be operationalized. Friends of Cancer Research (Friends) is convening stakeholders to curate data to determine how endpoints generated from real world data correlate with overall survival and other key indicators of disease burden from prior clinical trials. The group will use this data to help inform the development of a validation framework. This project will help inform ongoing regulatory discussions on the use of RWE by proposing a standard approach for data collection, as well as provide vital information about the long-term value of a product including its safety and efficacy.
For more information on this project, Click HERE.
Lung-MAP is a first-of-its-kind clinical trial model that uses a multi-drug, targeted screening approach to match patients with sub-studies testing investigational new treatments based on their unique tumor profiles.
The trial is a product of years of collaboration with government, leadership from the US Food and Drug Administration (FDA), National Cancer Institute (NCI), and National Institutes of Health (NIH), Foundation for the National Institutes of Health (FNIH), research institutions, patient advocacy groups, and industry, providing a model for more efficient, cooperative trials in the future.
Instead of having to undergo multiple diagnostic tests to determine eligibility for many different studies, enrollees are tested just once according to a “master protocol” and assigned to one of multiple trial sub-studies, each testing a different drug from a different developer.
- Patients are screened using a comprehensive genomic profiling platform that reviewed more than 200 cancer-related genes for genomic alterations.
- Based on the results of this screening, patients are assigned to whichever one of up to five sub-studies testing different investigational regimens best suits their genomic profile.
- This innovative approach improves a patient’s likelihood of receiving a drug that will work for them while allowing for new therapies in development to be added as the trial progresses.
The Lung-MAP trial has been active since 2014 and is enrolling patients across the country. To find a Lung-MAP site closest to you, go to www.lung-MAP.org and click HERE for more detailed information.
Breakthrough Therapy Designation
In 2012, the breakthrough therapy designation was signed into law with the help of Friends and other stakeholders. A new drug may be designated as a breakthrough therapy by the Food and Drug Administration (FDA) if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence suggests it provides a substantial improvement over existing therapies. Working with our partners in all sectors, Friends took ‘Breakthrough’ from concept, to scientific whitepaper, to bipartisan legislative solution, to a tool in full use by FDA to expedite the approval of multiple drugs in 13 months.
Friends Work Towards Breakthrough
- July 2011: Health Affairs Study - Despite criticism of the FDA review process, new cancer drugs reach patients sooner in the United States than in Europe.
- November 2011: Annual Meeting Panel - Development Paths for New Drugs with Large Treatment Effects Seen Early
- July 2012: Congress Passes the Food and Drug Administration Safety and Innovation Act (FDASIA), signing the Breakthrough Therapy Designation into law
- September 2012: Friends, Alexandria White Paper - A Risk-based Approach for In Vitro Companion Diagnostics Device FDA Approval Process Associated with Therapies that have Breakthrough Designation
- November 2012: Annual Meeting Panel - Developing Standards for Breakthrough Therapy Designation
- August 2013: Journal for Clinical Cancer Research article summarizing panel recommendations for FDA
Friends continues to monitor the success of the program, as well as its impact on patients and the drug development process. Click HERE to access an interactive list of current breakthrough therapy designations.
Manufacturing for Breakthrough Drug Development
With the passage of the Advancing Breakthrough Therapies for Patients Act in 2012, sponsors can expedite the development of promising treatments, yet drug manufacturing and characterization timelines have been put under significant strain to guarantee readiness at the time of marketing approval.
- Friends Forum - Examining Manufacturing Readiness for Breakthrough Drug Development
- November 2015 White Paper
Blueprint for Drug/Diagnostic Development
Since 2012, Friends and Alexandria Real Estate Equities, Inc. have been addressing the co-development of targeted therapies and companion diagnostic tests.
Beginning with the first Friends-Alexandria Blueprint Forum in 2012, each year we have been bringing together researchers, sponsors, advocates, and regulators to discuss the development of diagnostics for targeted therapies. This subject has significant implications for the development and use of precision medicines, many of which target narrow patient populations that can only be identified with diagnostic tests. As regulators and drug developers work to improve the speed at which promising new therapies reach patients, it has become more important than ever that diagnostic tests be developed and evaluated efficiently.
These topics have included adapting FDA guidance on companion diagnostics for Breakthrough Therapy designation, standardizing and expediting Next Generation Sequencing for companion diagnostic use and using genetic databases to facilitate drug/diagnostic development and improve patient care. These forums continue to drive policy changes through FDA guidance and legislation.
Patient advocates play a major role in shaping public policy, making a lasting impact in various domains. Advocates have secured increased support for government-funded biomedical research and created incentives for pediatric and rare disease drug development, to name a few. Through our new initiative on ProgressForPatients.org, Friends is bringing together those who seek solutions to advance science through engaging, educating, and empowering patients. Consisting of an online-education platform, Friends provides a primer on the FDA, drug development and regulatory policy, from the conduct of clinical trials to FDA review procedures, to enable advocates to better engage with policymakers.
In addition to our Advocacy Education program, Friends has a new initiative through ProgressForPatientsorg called the Advocacy Alliance. The Advocacy Alliance serves as a portal for organizations to stay informed on the most pressing policy issues, current proposals, and national priorities in regulatory science. The members only site provides resources and a platform for your organization to join Friends of Cancer Research as we engage Congress and federal health agencies on the latest issues.
To learn more about the Friends Advocacy Education program, the Advocacy Alliance, or request access, please visit ProgressForPatients.org.
Enhancing Use of Patient Experience Data
Incorporating the patient experience into drug development is a crucial next step to ensuring that those suffering with this disease are getting the safest and most effective treatments possible.
- Friends Roundtable White Paper - Enhancing Use of Patient-Centered Data in Regulatory Decision-Making
- Friends Annual Meeting Panel - Capturing Symptomatic Adverse Events From the Patients’ Perspective
Examining Use Trends of Biomarker Tests in Lung Cancer
Friends, in collaboration with the Deerfield Institute, is looking to better understand how patients are being tested in the real world. As the molecular understanding of cancer continues to advance, an increasing number of drugs have been developed to target subsets of patients based on specific genetic characteristics. Properly identifying which patients should receive these treatments can optimize healthcare resources and direct patients to the treatment options that have the potential to provide the greatest benefit. Through a survey completed by hundreds of oncologists around the country, Friends and the Deerfield Institute are studying how often patients with non-small cell lung cancer (NSCLC) are being tested for molecular alterations that, if present, make them candidates to receive targeted therapy.
Modernizing Eligibility Criteria
Friends, in partnership with the American Society of Clinical Oncology, is conducting a project to evaluate eligibility criteria in clinical trials. Eligibility criteria (EC) are necessary in clinical trials to define the patient population under study, isolate the potential effect of an investigational drug, and ensure that the trial is conducted safely. However, excessive or overly rigid criteria may impair the rate of trial accrual, restrict patient access to investigational drugs, and limit the ability to generalize the results to the broader population of patients who ultimately use the drug. The goals of this effort are to identify opportunities where trial eligibility can be broadened to improve patient access to investigational agents, the generalizability of trial results, and the accrual rate of cancer clinical trials.
Development and Implementation of Biosimilar Pathway
Friends, in partnership with the Duke-Margolis Center for Health Policy, is working to further define and improve the regulatory requirements for biosimilars, which are significantly greater than those for generic drugs. Despite FDA’s progress with guidance and approving the first biosimilar (Zarxio) in 2015, questions remain for the implementation of the biosimilar pathway in the US, particularly for the development of monoclonal antibody biosimilars, and clarity is still needed from the FDA regarding standards for demonstrating interchangeability.
A new partnership between Pfizer, EMD Serono, Friends, and SITC is looking at the overarching goal of identifying opportunities within the evolving field of immunotherapy and prioritize policy changes necessary to address challenges and accelerate progress for patients. By initially convening a small, but representative group of scientific, clinical, patient, policy and industry thought leaders to shape a multi-stakeholder process, this effort will develop an Immuno-Oncology strategic policy plan to accelerate progress across multiple oncology disease states.