“The TAPUR Study is unique in that it aims to identify potential new uses of marketed drugs based on a patient’s tumor genomic profile. By seeing how these therapies perform outside of their FDA-approved indication in real world populations, we can learn about potential new uses for these treatments.”
- Richard L. Schilsky, MD, FACP, FASCO, ASCO’s Chief Medical Officer
Precision medicine has revolutionized cancer care. Just look at non-small cell lung cancer (NSCLC), for example. In the past few years, researchers have learned much about the genomic alterations in NSCLC and have been able to develop new drugs to target them. There are now six categories of targeted therapies for NSCLC, each aimed at a different genomic profile of the disease: there are two drugs that target tumor blood vessel growth; three that target cells with epidermal growth factor receptor (EGFR) mutations; one specifically for an EGFR gene mutation known as T790M that confers resistance to first-generation EGFR inhibitors; one EGFR inhibitor for squamous cell NSCLC; four drugs that target tumors with ALK gene rearrangements; and two drugs that target cells with BRAF mutations.1
Targeted therapies are becoming increasingly precise, and research into cancer biology is quickly enabling the development of drugs that fight cancer at the molecular level. Just last year new therapies became available for people with advanced blood, breast, kidney, and lung cancers.
Genomic profiling may reveal therapy options for patients, such as treatment with an investigational agent in a clinical trial or use of a targeted therapy approved by the Food and Drug Administration (FDA) for a different cancer. However, it’s often difficult for patients to get access to and reimbursement for anti-cancer agents used outside of FDA-approved indications. And when a patient receives a drug for a novel use outside of a clinical trial, the larger medical community does not get to learn whether that particular drug worked in that patient with those particular characteristics because current prescribing practices don’t capture the outcomes of patients who receive therapies off-label.
ASCO launched its Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a non-randomized clinical trial, in March 2016 to learn from the real-world practice of prescribing targeted therapies to patients with advanced cancers that harbor a genomic variant known to be a drug target. TAPUR’s unique pragmatic design is anchored in clinical practice, while maintaining the framework and standards of a clinical trial, and it provides FDA-approved drugs that are already in use at no cost to those enrolled in the study. The study launched at only 35 sites located primarily in two states and has now expanded to include 101 participating sites in 20 states.
Those enrolled in the study—367 patients as of mid-July—are followed for standard clinical outcome measures. The 17 drugs, which yield 15 different targeted therapy options (some drugs are used in combination) are contributed to the program by seven pharmaceutical companies: AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, Merck, and Pfizer. Treating physicians will collect data on clinical outcomes regarding antitumor activity of these treatments outside of indications already approved by the FDA. The 15 therapies are: axitinib (Inlyta®), bosutinib (Bosulif®), cetuximab (Erbitux®), crizotinib (Xalkori®), dasatinib (Sprycel®), erlotinib (Tarceva®), olaparib (Lynparza®), palbociclib (Ibrance®), pembrolizumab (Keytruda®), regorafenib (Stivarga®), sunitinib (Sutent®), temsirolimus (Torisel®), trastuzumab (Herceptin®) and pertuzumab (Perjeta®), vemurafenib (Zelboraf®) and cobimetinib (Cotellic®), and vismodegib (Erivedge®).
Treatments under investigation in the TAPUR Study are dispensed to eligible participants in accordance with FDA-approved dosing, and any necessary dose modifications are determined by the treating physician within the guidelines of the TAPUR Study protocol. Patients who receive drugs on the protocol are followed for standard toxicity and efficacy outcomes, including tumor response, progression-free and overall survival, and treatment duration.
For physicians, the trial is designed to be pragmatic, allowing them to choose the tumor specimen or blood sample and genomic profiling test to be performed; apply broad general eligibility criteria; and streamline data collection. The TAPUR Study will also provide the opportunity to capture each patient’s outcomes with a particular drug or drug combination so that other patients and oncologists can learn how these targeted agents are working to treat other cancer types. This is in contrast to current prescribing practices, which don’t capture the outcomes of patients who receive therapies off-label.
The patients enrolled in the study have advanced solid tumors, B cell non-Hodgkin lymphoma, or multiple myeloma with a genomic variant known to be a drug target or to predict sensitivity to a drug. They also have undergone and received results from a genomic test that demonstrates that a relevant genomic variant is present in the cancer.
There is specific genomic inclusion and exclusion criteria included for each drug outlined within the TAPUR Study protocol. The TAPUR Study database includes an electronic algorithm of these “rules” to “match” a patient’s tumor to a treatment. The oncologist proposes a treatment in accordance with these rules and inputs it into the TAPUR Study database.
If the treating physician would like to propose a match outside of the TAPUR Study rules or a physician needs further guidance, he or she can consult the TAPUR Molecular Tumor Board, which can then identify TAPUR Study drugs or other options based on the tumor genomics. The board, which is comprised of a group of experts convened by ASCO, reviews and discusses cases that do not fit the criteria specified in the protocol, as well as cases where the treating physician requests guidance. If the board cannot identify an appropriate option within the drugs available in the TAPUR Study, it may be able provide information on alternate ongoing clinical trials for consideration. If a TAPUR Study drug option is identified, the ultimate decision to enroll in the study will be made by the patient and the treating physician.
The trial has been designed to be as streamlined as possible to maximize the number of potential patients while minimizing the reporting burden for physicians. For patients, the study has broad eligibility criteria. For physicians, they have discretion on genomic testing, drug dosing, and dose modifications. The study requires only the minimum amount of required data collection necessary in order to meet study objectives, and there are rigorous data validation procedures and processes without traditional auditing or monitoring.
ASCO has partnered with the Research Advocacy Network to educate oncologists about implementing precision medicine in clinical practice. A sub-study will assess how tumor genomic testing is being used by clinical oncologists and how best to provide assistance with provider and patient education.
In June, ASCO announced that the TAPUR Study is expanding its reach globally by collaborating with two organizations that have studies in development that are based on the TAPUR Study: the Canadian Cancer Trials Group (CCTG) and WIN Consortium. ASCO aims to collaborate with these two groups to share study results to accelerate learning. WIN Consortium—a global network of renowned academic cancer centers, pharmaceutical and diagnostic companies, and patient advocacy organizations spanning 16 countries and four continents—will offer an opportunity to expand a version of the TAPUR study to more than a dozen countries outside of North America. WIN will be deploying WIN_TAPUR in the following countries: Brazil, China, Denmark, France, India, Israel, Japan, Jordan, Luxembourg, Russian Federation, Singapore, South Korea, and Spain. Another protocol similar to TAPUR, the DRUP (Drug Rediscovery Protocol) study, also is ongoing in the Netherlands and data from this study is also intended to be shared with the TAPUR study.
The TAPUR Study is registered on ClinicalTrials.gov (NCT 02693535), which includes a full list of inclusion/exclusion criteria and other information, as well as study information such as general eligibility criteria and participating clinical sites.
Additional information can be found on the TAPUR study website, where there is also a video that provides an overview of the TAPUR study.