TAPUR: ASCO’s First Clinical Trial Addresses Critical Gaps in Understanding of and Access to Targeted Therapies

ASCO is preparing to expand the boundaries of precision medicine with the launch of its first clinical trial. At a press briefing during the 2015 ASCO Annual Meeting, the Society formally announced its plans for the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

At a time when physicians are frequently confounded by how to act on the results of genomic testing to benefit their patients, TAPUR and similar investigations are critical. “We have a big knowledge gap and an unbelievable opportunity,” said ASCO Past President Clifford A. Hudis, MD, FACP, of Memorial Sloan Kettering Cancer Center, who moderated the press conference.

Rationale and Design

ASCO recognized two significant challenges slowing the pace of discovery in precision medicine: a lack of access to drugs prescribed off label and a lack of data collection on the safety and efficacy of such treatments. TAPUR has the potential to address both issues, by making targeted drugs available to participants at no cost and by creating a registry 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 based on such tests remain largely anecdotal or unknown,” said ASCO Chief Medical Officer ­Richard L. Schilsky, MD, FACP, FASCO, who is leading the study (see related article).

The prospective, nonrandomized TAPUR clinical trial will collect information on the antitumor activity and toxicity of commercially available targeted cancer drugs in a range of cancer types (including advanced solid tumors, multiple myeloma, and B-cell non-Hodgkin lymphoma) with a genomic variation known to be a drug target.

At its outset, TAPUR will evaluate 10 to 15 drugs contributed by five pharmaceutical companies, with cohorts of up to 35 patients defined by tumor type, genomic abnormality, and drug. Patient enrollment is expected to open in early 2016.

Patients will be screened to determine if they are healthy enough to participate based on broad inclusion/exclusion criteria. If and when a patient meets the defined trial criteria, the 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 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 case and suggest potential therapies on or off the study.

The primary endpoint of TAPUR is objective tumor response defined by RECIST or stable disease for at least 16 weeks; other endpoints include progression-free survival, overall survival, duration of treatment, and treatment-related serious adverse events.

Practical Applications of TAPUR

TAPUR will harness information from discussions about molecular targets and potential treatments that are already happening in oncology practices every day—a source of knowledge that is currently lost, because there is no mechanism to learn from the experience of patients who use targeted drugs in off-label settings, Dr. Schilsky said.

Edward S. Kim, MD, confirmed that in his practice, patients and their family members frequently ask about the effectiveness of targeted therapies and request commercially available marker panels to assess their tumors.

“The truth is that scientists and clinicians don’t know what to do with many of these markers. We have no idea how impactful they are when applying a therapy. Sometimes, physicians have to make independent decisions based on their own knowledge. Sometimes, there are opportunities to use a molecular tumor board to have a forum discussion about markers and treatments. But we’re all still learning. There is no instruction booklet that tells us, ‘If A, use B.’ The levels of evidence vary, and there can be a lot of bias in the decision-making. Capturing this information prospectively and being able to analyze outcomes based on drug selection are the best ways to start making better informed decisions moving forward,” he said.

Dr. Kim is Chair of Solid Tumor Oncology and Investigational Therapeutics at Levine Cancer Institute, Carolinas HealthCare System, one of the three clinical sites at which TAPUR will launch. He is a veteran of personalized medicine studies, having served as lead investigator for the BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination) trial while at The University of Texas MD Anderson Cancer Center.

From a clinical perspective, he believes, the most exciting aspect of ­TAPUR is access. Too often, a panel will yield an interesting marker in a patient’s tumor for which there is a drug that may be effective, but the drug is not approved or indicated for that particular setting.

“The patient is put in an impossible position. Should they divest their life savings…and spend tens of thousands of dollars to try a drug for a few months? Should they appeal to the drug company and spend months trying to get access to the drug?” Dr. Kim explained. Because selected targeted therapies will be made available to TAPUR participants at no cost, “we don’t have to ask our patients to make that choice. That access is incredible.”

A Collaborative Effort

Numerous partners have contributed knowledge, expertise, and resources to make TAPUR possible. ASCO will sponsor and organize the operational aspects of the study, including the participation of multiple collaborators.

Cancer researchers and patient advocates are important partners in the study and will contribute to the planning and conduct of TAPUR, as well as assist in increasing public and patient awareness. Jane Perlmutter, PhD, a cancer survivor and nationally recognized patient advocate, is lending her expertise in trial development and will help coordinate patient advocate recruitment and training for the study.

TAPUR will launch at clinical sites within the Michigan Cancer Research Consortium, the Cancer Research Consortium of West Michigan, the Levine Cancer Institute, and the Carolinas HealthCare System, with the goal of expanding nationally.

ASCO has invited a number of pharmaceutical companies to provide marketed, targeted drugs and additional resources to support TAPUR. Five companies have signed memoranda of understanding agreeing to participate in the study as of July 2015: AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, and Pfizer.

“At least 13 drugs that target more than 20 unique genomic variants will be provided by these companies. We are extremely grateful for the generosity of these companies without whose support ­TAPUR would not be possible,” said ASCO Immediate Past President Peter Paul Yu, MD, FACP, FASCO. “We anticipate additional companies will sign on, and we are extremely encouraged by the level of interest we have received so far.”

Two technology companies will provide key support to the study’s data collection: Syapse and Illumina. Syapse will provide its Syapse Precision Medicine Data Platform to automate the study workflow (including the Molecular Tumor Board and the Data and Safety Monitoring Board) and capture structured data from participating practices. Illumina will provide its NextBio knowledge base platform to support and inform the case review by the Molecular Tumor Board, as well as to support analysis of TAPUR data by the study team.

ASCO will collaborate and share data from TAPUR with the Netherlands Center for Personalized Cancer Treatment, which is conducting a clinical trial using a very similar study protocol.

For more information on ASCO’s Targeted Agent and Profiling Utilization Registry, visit asco.org/TAPUR. Online resources include a fact sheet, frequently asked questions, tools for patients and patient advocates, and recent publications about the study. ■