Off-Label Access to Targeted Therapies Offered Through ASCO's First-Ever Clinical Trial

Richard L. Schilsky, MD

Physicians will now have a new option for some patients who have run out of them, but whose tumors have a genomic variation matching a drug target that is FDA-approved for a different cancer.

ASCO unveiled its first clinical trial, known as TAPUR, June 1 in a press briefing at the organization’s 2015 Annual Meeting with the aim of simplifying patient access to cancer treatments across many tumor types. TAPUR (Targeted Agent and Profiling Utilization Registry) focuses on community-based research programs where the majority of patients are treated.

The nonrandomized clinical TAPUR trial will involve patients with any advanced solid tumor, multiple myeloma, or non-Hodgkin lymphoma that has a genomic variation known to be a drug target.

The primary objectives of TAPUR are twofold, explained ASCO’s chief medical officer, Richard L. Schilsky, MD, FACP, FASCO, at the press briefing: to improve access to potentially effective therapies for a much broader population than is typically enrolled in clinical trials, and to gather important information on the antitumor and toxicity of targeted drugs across multiple cancers.

“Increasingly, we find that patients with advanced cancer who no longer have any standard treatment options are having a genomic profiling test performed,” noted Schilsky in explaining the rationale for the initiative. “These tests are now readily available…and sometimes what’s known as ‘a potentially actionable variant’ is detected.”

Estimates in the literature are highly variable, he added, but about 40% to 70% of the time these tests are likely to turn up something that the doctor might be able to act on: “The question that the doctor and the patient then face is, ‘How do I get the drug that is suggested by my tumor’s profile?’”

Although in some cases, the drug will be investigational and thus best administered in the context of a conventional clinical trial, “in other cases, given the large number of targeted therapies that are now commercially available, the best option for the patient might be to receive a commercially available targeted drug, but one that would have to be prescribed outside of its FDA-approved indication,” a process that can be very complicated and burdensome.

A Collaborative Effort

Even when patients do get access to these agents, said Schilsky, “we have no mechanism right now to learn the experience of that patient—how the patient did, whether they responded or not, whether they had side effects—that information is never captured in any organized way that we as an oncology community can learn from.”Five pharmaceutical companies (AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Genentech, and Pfizer) have signed on to provide their currently marketed targeted drugs at no charge to participants, and more are expected to join the effort, noted ASCO President Peter Paul Yu, MD, FACP, FASCO, in a statement. He added that “at least 13 drugs that target more than 15 genomic variants will be provided by these companies.”

Data analysis will be provided by two technology companies, Syapse, who will automate the study workflow, and NextBio, who will support and inform the case review.

Patient advocates also will be providing guidance and oversight support for TAPUR. Jane Perlmutter, PhD, a cancer survivor and nationally recognized patient advocate, will help coordinate patient advocate recruitment and training for the initiative.

“TAPUR has enormous potential to improve our understanding of the effectiveness of currently available therapies in treating cancers with genomic variations and to learn from patients who are treated with off-label drugs,” said Perlmutter in an ASCO statement, adding that the program will be especially helpful “for those with advanced cancer for whom traditional therapies are no longer working.”

Timetable and Protocol

ASCO also is collaborating with the Netherlands Center for Personalized Cancer Treatment which is conducting a clinical trial using a study protocol very similar to TAPUR.Schilsky said that ASCO will submit its completed trial protocol and consent form to an institutional review board in July, and the organization hopes to begin patient enrollment by the end of this year.

He said the patient eligibility criteria are intentionally broader than that of a typical clinical trial. The study will enroll patients with advanced solid tumors, B-cell non-Hodgkin lymphoma, and multiple myeloma who are not responding to standard anticancer treatment or for whom no acceptable treatment is available. Patients will be screened to determine if they have adequate organ function to participate based on broad inclusion/exclusion criteria.

Any genomic test that is available to the physician in clinical practice, as long as it is performed in a CLIA-certified/CAP-accredited laboratory, will be enough to qualify a patient to enter the study, Schilsky said.

If a patient meets the trial criteria, his or her physician can select a drug from among those available in the TAPUR study protocol that targets the genomic variation in the patient’s tumor. Physicians can consult one of ASCO’s three oversight committees set up for the initiative, the Molecular Tumor Board, for guidance on potential therapies on or off the study, if a relevant drug match is not described in the protocol. ASCO also will have a Steering Committee and Data and Safety Monitoring Board to oversee the effort.

All patients who receive treatment through TAPUR will be monitored for standard toxicity and efficacy outcomes, including objective response rate per RECIST criteria—the study’s primary endpoint—as well as time on treatment and progression-free and overall survival.

Schilsky explained that the unit of evaluation in the study will be a “tumor type genomic variant drug group.” The plan is to enroll eight patients per group; if no responses are observed, enrollment in that group will be stopped, but if there is at least one response, enrollment will be expanded up to a total of 24 patients.

“The idea here is to detect a signal of drug activity…we hope that signals of activity will result in pharmaceutical companies, the clinical oncology research community, or others pursuing those signals,” he continued.

TAPUR will be launched initially at three clinical sites—the Michigan Cancer Research Consortium, the Cancer Research Consortium of West Michigan, and the Carolinas Health System—with the ultimate goal of expanding the effort nationally.

More information about the program can be found at www.tapur.org.

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