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ASCO Expands TAPUR Sites; Inks Collaborations to Investigate Precision Oncology Globally

CHICAGO (GenomeWeb) – The American Society of Clinical Oncology has expanded the Targeted Agent and Profiling Utilization Registry (TAPUR) study to around 100 sites in the US, and inked collaborations that will also bolster other countries' ability to explore precision oncology hypotheses.

At the ASCO annual meeting here yesterday, the oncology group said that as of May 31, more than 300 patients had enrolled in TAPUR ― a non-randomized basket study investigating the safety and efficacy of commercially available cancer drugs when they are given off label and based on the genomic characteristics of patients' tumors.

When the study launched over a year ago, TAPUR was enrolling patients into 35 sites. But in the coming months eight new centers at 36 locations will begin to recruit patients, increasing the number of study sites to more than 100 in 20 US states. These sites will offer patients the chance to enroll in study arms investigating 15 targeted treatment options that seven drug companies have provided.

As part of its strategy to expand recruitment efforts, ASCO lowered the eligibility age from 18 years down to 12 years, so that adolescent patients with advanced cancer could join the study. Additionally, ASCO partnered with the Canadian Cancer Trials Group and the WIN Consortium, which are developing studies based on the TAPUR basket design. ASCO, WIN, and CCTG will share study results to improve understanding of genomically defined treatment strategies.

So far, TAPUR has matched 60 percent to 65 percent of patients to treatment arms, ASCO Chief Medical Officer Richard Schilsky said.

Basket trials have found it difficult to match patients to treatment arms. For example, the NCI-MATCH trial had to go on a hiatus last year because the interest in the study far outpaced the number of patients that matched to the 10 treatment arms that were initially available. The study reopened on May 31, 2016 with 24 treatment arms, and still there is a wide gap between the number of patients getting genetically tested and the proportion of patients getting on a matching treatment.

As of April 30, out of 4,800 patients who had genetic testing with NCI-MATCH, around 860 patients had a gene abnormality matching available therapy, and around 580 patients enrolled in a treatment arm. The study organizers estimate that 72 percent of patients assigned to a treatment arm ultimately enroll.

Some of the challenge is due to the state and complexity of the science, and some experts believe that matching rates within basket studies will improve as researchers identify more targetable alterations. Access to targeted treatments and the ability to standardize genomic testing are two other factors that have challenged basket studies to date, and Cure-One, an organization previously called MED-C, is hoping to help TAPUR with the latter.

“Two of TAPUR's largest challenges were getting patient[s] access to molecular testing and not being able to standardize the testing,” according to Cure-One CEO Dane Dickson, and this has raised questions about how variability in testing would impact the ability to interpret the effectiveness of the precision oncology approach on patient outcomes.

Cure-One runs the so-called N1 Registry, which aims to provide patients access to quality NGS testing, collects data that can improve understanding of genetic markers in cancer, and tracks how genetic testing is being used in the real world and impacting patient outcomes. The organization has partnered with ASCO to help enroll patients into TAPUR through its registry. "The expected size of the N1 Registry, [from] thousands to tens of thousands of patients, should allow fertile ground for finding patients for targeted trials," Dickson said.

Cure-One recently announced that Foundation Medicine and Guardant Health will be the approved labs within the N1 Registry that will provide NGS testing for solid tumors and liquid biopsies for enrolling patients. The partnership with ASCO, for the time being, would allow patients in the registry to be evaluated for potential enrollment into TAPUR. "The eventual goal would be to have some direct connection between the N1 Registry testing results to pre-screen patients for TAPUR inclusion, but this is something that will be discussed in the future," Dickson said.

Meanwhile, ASCO is directly working with Foundation Medicine and Caris Life Sciences within the TAPUR study. The NGS test providers are the first labs that will provide a report identifying genomic alterations of interest in TAPUR, so that study sites can easily identify the variants that would allow patient enrollment.

TAPUR is further challenged by the fact that the matrix of the trial is huge. "You have all the different tumors, then the genetic events, and the drugs," said Vladimir Lazar, chief scientific and operating officer at the WIN Consortium. With so many cohorts, "from a statistical point of view, in order to have proof of efficacy you will need a lot of time and patients."

ASCO's partnership with CCTG and WIN Consortium will extend access to genomically informed, off-label treatment approaches through basket studies in countries outside of the US. WIN is a global network of cancer centers, pharmaceutical and diagnostic companies, and patient advocacy organizations in 16 countries across four continents. The consortium will deploy WIN-TAPUR in Brazil, China, Denmark, France, India, Israel, Japan, Jordan, Luxembourg, Russia, Singapore, South Korea, and Spain.

There has been enormous interest outside of the US to enroll cancer patients into TAPUR-type studies as a way to explore efficacy and safety of treatments given off label. "In the US, use of drugs off label is allowed," Lazar said. "But in other countries this is not allowed by regulatory bodies."

For example, in France, where Lazar is based, in order to treat a colon cancer patient with a BRAF mutation with Genentech's Zelboraf (vemurafenib), a drug approved in BRAF-mutated melanoma, he said it would require a special request to the regulatory authorities and a large data dossier, and then the regulators would take a long time to decide on the application.

"But if this is handled like a clinical trial it is huge progress toward globally-driven precision oncology," Lazar said. "This may have a fabulous impact on knowledge, but also on patients."

ASCO will also share data with the Netherlands Center for Personalized Medicine, which is conducting an independent study protocol similar to TAPUR, called the Drug Rediscovery Protocol trial, and will work with the Research Advocacy Network on a substudy to garner insights into how genomic testing is being used by clinical oncologists. Around 100 doctors in 54 TAPUR sites are participating in the substudy.

Syapse has also been using its Precision Medicine Platform to automate patient data capture from electronic medical records of participating practices and match them to TAPUR treatment arms based on genomic characteristics. The medical technology firm will now perform automated matching for TAPUR within Syapse Oncology, a software suite that allows health systems to scale precision oncology programs, which would also cast a wider net for identifying study participants.