The rapid pace of patient enrollment in the National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH or EAY131) precision medicine cancer treatment trial will result in the study reaching its goal of sequencing the tumors of 6,000 patients in June, nearly two years sooner than expected. The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN), which is leading this signal-finding trial under the sponsorship of the National Cancer Institute (NCI), reports that wide-scale adoption throughout the NCI National Clinical Trials Network (NCTN) and NCI Community Oncology Research Program (NCORP) caused the unprecedented rate of patient enrollment.
"NCI-MATCH's availability through more than 1,100 academic cancer centers and community hospitals reflects the broad interest in the promise of genomics, and the ability of such a study to deliver that promise to the community," said ECOG-ACRIN study co-chair Peter J. O'Dwyer, MD, University of Pennsylvania.
The more than 1,100 trial sites are all members of the research groups in the NCTN that design and lead trials focused on adult cancers: the Alliance for Clinical Trials in Oncology, ECOG-ACRIN Cancer Research Group, NRG Oncology, and SWOG.
"An important discovery in the patients we have tested so far shows us that every tumor gene abnormality we are studying is less common than expected in this study population, ranging from 3.47 percent to zero," said ECOG-ACRIN study chair Keith T. Flaherty, MD, Massachusetts General Hospital Cancer Center.
"This finding adds to the ground-breaking nature of the NCI-MATCH trial, which is shedding new light on the fact that for several of the treatment arms to reach their 35-patient goal, we really need to look at tens of thousands of patients," he said.
The NCI-MATCH trial had a goal to ensure that 25 percent of patients enter with rare or uncommon cancers, defined as those other than colorectal, breast, non-small cell lung, or prostate.
"We are surprised that over 60 percent of patients came into the trial with less common types of cancer, which far surpassed our goal," said Dr. O'Dwyer. "We find it exciting that this high proportion of less common malignancies opens options for advances in these cancers."
Another contribution to the rapid accrual rate was the availability--within the trial--of tumor gene sequencing for every patient who submitted tissue for testing. The NCI provided funding to reimburse participating sites for biopsy procedures and paid for the tumor gene sequencing performed by the trial's four-laboratory network, assembled especially for this trial.
New Trial Collaborations
Tumor sequencing within the trial is capped at 6,000 patients for the purpose of determining study eligibility. For the next several weeks, patients who registered for tumor screening before the deadline of May 22, 2017, will complete the process. Then, tumor testing within the trial will come to an end.
Even though tumor gene testing will no longer be done within the trial, the trial is not ending. It continues with a new study entry process that casts a wider net for patients through collaborations with commercial and academic laboratories.
"We have found a way to move the trial toward real-world genomic analysis of tumors," said Dr. O'Dwyer. "It's becoming more common for oncologists to order genomic tumor testing to guide clinical care for our patients. This is an optimal time to align the trial with this current practice as a strategy to proactively seek out additional patients."
To complete patient enrollment to multiple treatment arms, ECOG-ACRIN is implementing collaboration agreements formed by the NCI with Caris Life Sciences® and Foundation Medicine, Inc., two of the largest private-sector molecular testing laboratories. Collectively, these labs conduct sequencing for tens of thousands of people with cancer.
The collaboration agreements between the NCI and commercial labs are for Caris Life Sciences and Foundation Medicine, Inc. to notify any physician at any of the more than 1,100 clinical sites participating in NCI-MATCH when the genomic test they ordered to guide clinical care (Caris Molecular Intelligence®, FoundationOne®, or FoundationOne® Heme) finds results that could make a patient eligible for one of several NCI-MATCH treatments.
"These new collaborations offer a paradigm shift, as the new goal for the trial is to find patients, rather than patients having to find the trial," said Dr. Flaherty. "We look forward to incorporating this trial into the independent, routine testing already being done out in the community as soon as possible."
How They Work
The new study entry process is available to physicians at any participating site who order testing directly from the commercial laboratories. For participating sites, visit the NCI website.
The labs do not specifically test patients for the NCI-MATCH trial.
These labs will look for tumor gene abnormalities being studied in NCI-MATCH as part of their normal testing procedures. When a treating physician at a site that is participating in the trial orders genomic sequencing independently (outside of the trial) to guide clinical care for his or her patients, the labs will look for trial matches in these patients. If found, the lab will include the information in the broader genomic testing report as just one potential treatment option. The oncologist can take the information into consideration when discussing treatment options with his or her patients.
If a patient registers for NCI-MATCH, the physician will evaluate them further to determine if they meet the eligibility criteria for the specific treatment arm, and if so, the patient will be able to enroll for treatment. The trial's expert panel will review every patient case, as it has done since the start of the trial.
Trial leaders chose these labs because of their capabilities in three areas:
1. A mechanism that can review tens of thousands of patient cases is necessary to identify small subsets with tumor gene abnormalities being studied in the NCI-MATCH trial. These labs are already testing a high volume of patients.
2. Trial leaders have fully vetted the commercial assays and confirmed that the comprehensive and highly-validated genomic profiles are particularly sensitive to the tumor gene abnormalities being studied in the trial.
3. Collaboration requires that the labs provide assay results in a format that can be uploaded into MATCHbox, the trial's informatics system that generates treatment assignment information for the trial's panel of experts to review.
Two academic laboratories already involved in the trial will perform testing on their own patients, using their institutional assays. These are The University of Texas MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center.
The new study entry process will ramp up with a demonstration project focusing on 19 arms.
To help the trial adjust to the high volume of patient cases, the labs will initially report on only 19 of the 26 treatment arms still seeking patients. Each of the 19 arms addresses a tumor gene abnormality that occurred in 1.5 percent or fewer patients tested thus far. The potential for the outside labs to report on the remaining open treatment arms will be considered later in the summer once the demonstration project is complete.
To learn the status of each treatment arm, visit http://www.ecog-acrin.org/trials/nci-match-eay131.
About the NCI-MATCH Trial
NCI-MATCH is a phase II precision medicine trial that seeks to determine the effectiveness of treatment that is directed by genomic profiling in patients with solid tumors, lymphomas (cancer in the cells of the immune system), or myelomas that have progressed following all standard treatments expected to prolong overall survival or rare cancer types for which there is no standard treatment. The study attempts to demonstrate that matching certain drugs or drug combinations in adults whose tumors have specific gene abnormalities will effectively treat their cancer, regardless of its type. Such discoveries could be eligible to move on to larger, more definitive trials.
NCI-MATCH is unique because of its size and scope. It explores far more tumor gene abnormalities and drugs than any other precision medicine cancer treatment trial. It includes a large number of cancer types where most other trials address a single cancer. The drugs and drug combinations chosen for the trial have either been approved by the FDA for specific cancer types or are still being tested in other clinical trials but have shown some effectiveness against tumors with a particular gene alteration(s).
"There continues to be a high level of interest in the scientific potential of NCI-MATCH among patients, oncologists, and the pharmaceutical companies that make their drugs available for testing as part of the trial," said Dr. Flaherty. "The drugs and drug combinations we are exploring in NCI-MATCH are being studied for the first time across many cancer types."
The trial's main eligibility requirements for patients remain unchanged with the new process for study entry. The trial is for adults 18 years of age and older with any type of solid tumor, lymphoma (cancer in the cells of the immune system), or myeloma that has returned or gotten worse after standard systemic therapy (oral or intravenous). Patients may also be eligible if they have a rare type of cancer for which there is no standard treatment.
Timeline for Reporting on Accrual Demographics in the 6,000 Screened Patients
It will take several weeks for all patients to have their biopsies, submit them for testing, and receive their gene sequencing results from the NCI-MATCH trial labs. By late summer, study leaders plan to complete their analysis of the genetic, disease, and demographic characteristics of the 6,000-patient cohort and submit the data to a peer-reviewed medical journal. Data could be published in early 2018.
Timeline for Reporting on Patient Outcomes Data
Reporting on individual arms will occur once there is complete response and toxicity data for at least 31 patients per arm. Each trial arm requires about eight months of follow-up after it completes enrollment, to determine if responses are durable, plus time for finalizing data and analysis. Secondary analyses will include examination of response by disease histology, individual variants, and other factors.
Confirmation by Trial Laboratory Network
The trial's laboratory network will confirm test results from the commercial and academic laboratories on patients' archived specimens. These results will be returned to the clinician, but will not affect or delay eligible patients' ability to enroll for treatment. The network includes the ECOG-ACRIN Central Biorepository and Pathology Facility at The University of Texas MD Anderson Cancer Center as the central intake facility for biospecimens and accompanying documentation. Four CLIA-approved molecular diagnostics laboratories are involved. They include the NCI Molecular Characterization Laboratory (Mickey Williams, PhD), Massachusetts General Hospital Center for Integrated Diagnostics (A. John Iafrate, MD, PhD), MD Anderson Cancer Center Molecular Diagnostics Laboratory (Stanley R. Hamilton, MD), and Yale University Tumor Profiling Laboratory (Jeffrey Sklar, PhD).
The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) co-designed NCI-MATCH with the National Cancer Institute (NCI) and is leading the trial, a role that involves coordinating the genomic testing and supporting nearly 1,100 cancer centers and community hospitals that are participating in the trial with training, laboratory services, trial assignments, biostatistical support, data management, auditing, quality control, and public awareness.
ECOG-ACRIN is a membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. ECOG-ACRIN comprises nearly 1,100 member institutions in the United States and around the world. Approximately 12,000 physicians, translational scientists, and associated research professionals from the member institutions are involved in Group research, which is organized into three scientific programs: Cancer Control and Outcomes, Therapeutic Studies, and Biomarker Sciences. ECOG-ACRIN is supported primarily through NCI research grant funding, but also receives funding from private sector organizations through philanthropy and collaborations. It is headquartered in Philadelphia, Pa.
For more information, visit ecog-acrin.org or call 215.789.3631.