ASCO and NCI Launch Largest Precision Medicine Trials Using Real-World Evidence

August 2015 Vol 8, Special Issue: Payers' Perspectives in Oncology
Audrey Andrews

With better understanding of the biological underpinnings of cancer, precision medicine has evolved beyond a mere concept to an actual, real-world pursuit.

At a press briefing at ASCO 2015, Clifford A. Hudis, MD, immediate past president of ASCO and Chief, Breast Medicine Service, Memorial Sloan Kettering Cancer Center, NY; and Richard L. Schilsky, MD, Chief Medical Officer of ASCO, discussed ASCO’s Targeted Agent and Profiling Utilization Registry (TAPUR) study. James H. Doroshow, MD, Deputy Director for Clinical and Translational Research, National Cancer Institute (NCI), detailed the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) trial.

The trials will pair a patient’s tumor molecular profile with drugs that target those tumor variants. “Almost every cancer could be seen as a rare cancer with unique tumor characteristics. We are announcing the expansion of an ongoing dream we have been pursuing,” Dr Hudis said.

The aim is to study the tumor match approach in patients who have exhausted standard treatment options and for whom there is a relevant drug.

“To deliver on the promise of precision medicine, we will test drugs based on the biology of the cancer, not the anatomic source,” Dr Hudis said, noting that these trials are “a dramatic shift” and a “paradigm move in the field.”

Dr Schilsky added that the trials will solve a growing problem for oncologists—how to interpret the results of molecular testing. “Sometimes, the best option may be an available drug prescribed outside of its FDA-approved indication….Even if the patient can receive the drug, we have no mechanism for learning from the experience of that patient,” he said.

TAPUR Launching This Fall

“That’s what we designed TAPUR for, so we can learn from the real-world practice of prescribing targeted treatments,” Dr Schilsky said.

More than 30 commercially available drugs target molecular pathways that are frequently aberrant in tumors, and many more are in development. The TAPUR trial will match tumor profiles with available agents (used off label); the NCI-MATCH will go a step further to allow the use of a few agents in the pipeline as well.

Beginning in fall 2015, TAPUR will enroll patients with advanced solid tumors, B-cell non-Hodgkin lymphoma, and multiple myeloma from 3 healthcare systems. A molecular tumor board will review the proposed drug–target match and report to the physician on potential treatments, on or off the study. When the patient is enrolled and receives treatment, safety and efficacy outcomes will be recorded. TAPUR’s primary end point is objective response rate (ORR).

Each drug that targets a tumor and its identified genomic variation becomes a “group,” and there will initially be 8 patients per group. If no patient with a certain variant responds to the given drug, the group is discontinued. If at least 1 patient responds, an additional 16 patients will be enrolled in the group; if at least 5 patients within this 24-patient group respond, the drug will be evaluated further in this tumor-variant population.

Clinical launch sites include the Michigan Cancer Research Consortium, the Cancer Research Consortium of West Michigan, and the Carolinas HealthCare System. Partnerships have been established with 5 companies that will supply 13 drugs, including AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, and Pfizer.

NCI-MATCH in 2400 Sites

The NCI-MATCH trial will be larger and be available to more physicians. NCI-MATCH, in fact, “is the largest, most rigorous precision oncology trial in history,” Dr Doroshow announced.

The study, which launched during the ASCO meeting, will be conducted throughout the 2400-site network. It is expected that 3000 patients will be screened to find 1000 patients with mutations allowing a treatment match.

The ORR will be the primary efficacy measure. Initially, the investigators will focus on 10 substudies of the mutation variants and treatment arms, but this number will soon increase to more than 20. The initial studies and mutations are:

  • Crizotinib in ALK rearrangement
  • Crizotinib in ROS1 translocations
  • Dabrafenib plus trametinib in BRAF V600E or V600K mutations
  • Trametinib in BRAF fusions, or non-V600E or non-V600K BRAF mutations
  • Afatinib in EGFR-activating mutations
  • Afatinib in HER2-activating mutations
  • AZD9291 in EGFR T790M mutations and rare EGFR-activating mutations
  • Ado-trastuzumab emtansine in HER2 amplification
  • Defactinib in NF2 loss
  • Sunitinib in cKIT mutations.

Potential Benefits

As Dr Hudis pointed out, these studies are a means of learning more about biologic targets and the relevant drugs for them using fewer patients and at lower costs than conventional trials. In addition, patients will receive the targeted agents matched to their unique molecular profile. Physicians will receive interpretation of molecular test results, guidance in treatment recommendations, access to drugs, and clinical data on off-label use. The pharmaceutical industry will receive data on drug use and outcomes to inform research and development. And regulators will receive data on the extent and outcomes of off-label drug and testing use along with real-world safety data.

“We think that if TAPUR succeeds,” Dr Schilsky said, “benefits will be accrued to all stakeholders.”

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