Oct 24, 2016
ASCO opened participant enrollment for the Targeted Agent and Profiling Utilization Registry (TAPUR) Study in March 2016, marking a major milestone in the conduct of the Society’s first-ever clinical trial.
The prospective, nonrandomized TAPUR study is designed to explore and expand the boundaries of precision medicine. ASCO recognized two significant challenges slowing the pace of discovery in the field of targeted therapies: a lack of data collection on the safety and efficacy of using approved drugs for other cancers, and a lack of access to such treatments.
TAPUR addresses both issues by making targeted drugs available to study participants at no cost and by creating a prospective study database to record and share key clinical outcomes.
“Clinical reports, to date, suggest that 30% to 80% of advanced solid tumors harbor potentially actionable genomic variants, but the outcomes of patients treated with therapies targeted at these variants remain largely anecdotal or unknown,” said ASCO Chief Medical Officer Richard L. Schilsky, MD, FACP, FASCO, who is leading the study.
TAPUR is a pragmatic clinical trial that uses drugs already approved by the U.S. Food and Drug Administration (FDA) to target genomic variants for certain cancers and collects information from routine clinical practice about therapeutic application to other cancer types with the same molecular targets. With expanded access to genomic testing, outside of the FDA-approved use, these targeted drugs are already being delivered in oncology practices every day. Information from these patients’ experiences is rarely captured because there is no mechanism to gather the clinical outcomes. TAPUR, however, offers this opportunity.
TAPUR exemplifies the concept of personalized medicine by using biomarkers to direct therapy, explained Jane Perlmutter, PhD, a member of the TAPUR Steering Group and the TAPUR Molecular Tumor Board. “TAPUR attempts to test a variety of drugs that have already been shown to be efficacious for some patients with particular biomarkers. The concept of TAPUR is that the biology of a cancer, rather than its organ site of origin, may be more useful in predicting whether a drug will be effective,” she said. “One advantage of the study is that we already know a great deal about the toxicity of the TAPUR drugs since the FDA has already approved their use in some cancer settings. Receiving a drug that is targeted to the biology of your own cancer, that already is known to be helpful to patients with similar cancer biology, and that has a reasonable toxicity profile makes this a wonderful trial for patients who qualify.”
Because of its unique design and purpose, TAPUR is including a broader patient population than that of most clinical trials. TAPUR is open to patients age 18 or older who have an advanced solid tumor, multiple myeloma, or B-cell non-Hodgkin lymphoma that is no longer responding to standard anticancer therapy or for which no acceptable standard treatment is available. Patients must have a genomic variant known to be a target of one of the 17 TAPUR drugs, per the study protocol.
For patients who meet the defined trial criteria, their treating physician will select a drug from among those available in the TAPUR study protocol that targets the identified genomic variation in the patient’s tumor. If a clinically relevant drug–target match is not described in the protocol, the physician may consult the TAPUR Molecular Tumor Board, which will review the clinical and genomic features of the participant’s case and suggest potential therapies on or off the study.
Each specific combination of tumor type, genomic variant, and study drug will form a cohort for analysis in the study. For each cohort, 10 participants will initially be enrolled. In groups where at least two participants respond to therapy, enrollment will expand by an additional 18 participants. The primary endpoint is objective response or stable disease for at least 16 weeks. Participants are followed for standard toxicity and efficacy outcomes, and data on antitumor activity and toxicities are collected for analysis and reviewed by an independent Data and Safety Monitoring Board.
In addition to the Molecular Tumor Board and Data and Safety Monitoring Board, ASCO has established a Steering Group to oversee the trial. Patients and patient advocates are included in all groups and play a role in providing direction and guidance regarding all aspects of the study. Based on current enrollment, ASCO expects to present initial results in 2017.
Leading companies, research networks partner to support trial
ASCO launched the TAPUR study at more than 37 clinical sites within the Carolinas HealthCare System’s Levine Cancer Institute, Michigan Cancer Research Consortium, the Cancer Research Consortium of West Michigan, and the University of Michigan. ASCO plans to expand patient enrollment at additional sites throughout the country in late 2016 and 2017.
AstraZeneca, Bayer, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, Merck, and Pfizer are providing approved, targeted drugs at no cost to participants, as well as additional resources to support the study. Additional companies plan to participate as enrollment continues.
The successful launch of TAPUR across clinical research sites is a testament to ASCO leaders, volunteers, and partnering organizations, according to Edward S. Kim, MD, Chair of the TAPUR Steering Committee. “The feedback from our doctors has been very positive,” he said. “For example, Levine Cancer Institute, where I practice, has been a very successful model leading enrollment for the study. Although the study is complex, and requires integrating large biomarker panels with a variety of drugs, it has a practical clinical applicability that has allowed broad participation from clinical teams and patients.”
ASCO is using the Syapse Precision Medicine Platform to automate the study workflow. Study drugs are being dispensed through Cardinal Health Specialty Pharmacy. ASCO is collaborating with the Netherlands Center for Personalized Cancer Treatment, which launched a clinical trial using a study protocol very similar to TAPUR.
Physicians and patients can find study information, such as general eligibility criteria, participating locations, and contact information for the study team, at TAPUR.org. TAPUR is also registered on clinicaltrials.gov (NCT02693535), which includes a full list of inclusion/exclusion criteria.