Two Large National Personalized Medicine Clinical Trials Are Launched by ASCO and NCI
Chicago, IL—Precision medicine in oncology is now being studied in clinical trials in oncology. These trials will pair a patient’s tumor molecular profile with drugs that address those tumor variants.
At the 2015 American Society of Clinical Oncology (ASCO) meeting, 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.
“Almost every cancer could be seen as a rare cancer with unique tumor characteristics,” Dr Hudis noted. “We are announcing the expansion of an ongoing dream we have been pursuing.”
Researchers are moving beyond anecdotal successes of targeted therapies to study the tumor match approach in patients who have no additional treatment options available.
“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. And these trials are “a dramatic shift, a paradigm move in the field.”
“Sometimes, the best option may be an available drug prescribed outside of its FDA-approved indication. That leads to difficulties, [such as] access, lack of insurance coverage, and phone calls to payers and pharmaceutical companies begging for the drug. Even if the patient can receive the drug, we have no mechanism for learning from the experience of that patient,” Dr Schilsky said.
“That’s what we designed TAPUR for, so we can learn from the real-world practice of prescribing targeted treatments,” he said.
More than 30 drugs currently target molecular pathways with frequently aberrant tumors, and many more drugs are in development. The TAPUR trial will match the patient’s tumor profile with available drugs used off label. The NCI-MATCH trial will go a step further by using a few agents in the pipeline as well.
Hematologic Cancers Trial
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.
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 participating companies—AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech, and Pfizer—who will supply 13 drugs.
“We think that if TAPUR succeeds, benefits will be accrued to all stakeholders,” Dr Schilsky said.
Largest Personalized Medicine Trial
By contrast, the NCI-MATCH trial will be larger and 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 2015 ASCO annual meeting, will be conducted throughout the 2400 sites of the NCI-supported National Clinical Trials Network.
It is predicted that 3000 patients will be screened to find 1000 patients with mutations that facilitate a treatment match.
Initially, the investigators will focus on 10 substudies of the variants and treatment arms, but this number is expected to increase to more than 20 soon. The initial substudies will include the following agents for these specific molecular targets:
- Crizotinib (Xalkori) in ALK rearrangement
- Crizotinib in ROS1 translocations
- Dabrafenib (Tafinlar) plus trametinib (Mekinist) in BRAF V600E or V600K mutations
- Trametinib in BRAF fusions, or non-V600E or non-V600K BRAF mutations
- Afatinib (Gilotrif) in EGFR-activating mutations
- Afatinib in HER2-activating mutations
- AZD9291 in EGFR T790M mutations and rare EGFR-activating mutations
- Ado-trastuzumab emtansine (Kadcyla) in HER2 amplification
- VS-6063 (defactinib) in NF2 loss
- Sunitinib (Sutent) in cKIT mutations.
Future BenefitsThese and future precision medicine trials will benefit more than individual patients. As Dr Hudis pointed out, these studies are a means of learning more about targets and their drugs with fewer patients and at lower costs than conventional trials.
In addition, patients will receive the targeted agent matched to their 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 plans and life-cycle management. Regulators will receive data on the extent and outcomes of off-label drug and testing use along with real-world safety data.