Results from the Molecular Analysis of the Initial Screening Phase of the NCI-MATCH Trial

The goal of the NCI-MATCH (Molecular Analysis for Therapy Choice) clinical trial is to determine if a molecularly targeted treatment that is matched to a genetic abnormality in a patient’s tumor is effective regardless of tumor type. NCI-MATCH is available to all members of the four NCI National Clinical Trials Network (NCTN) adult groups and is open at more than 1,100 sites in the US across the NCTN and the NCI Community Oncology Research Program (NCORP). People who are over the age of 18 and have a refractory solid tumor, lymphoma, or myeloma can participate.

A recent publication in the Journal of Clinical Oncology (Flaherty, 2020) describes the molecular results of the initial screening phase of the trial, which analyzed the tumor biopsies of nearly 6,000 patients. The biopsies were subjected to targeted Next-Generation Sequencing of 250 genes that aligned with a targeted agent that had demonstrated anti-tumor activity against that abnormality.

The screening phase aimed to enroll patients on 24 study arms and reached its accrual goal by May 2017, which was two years ahead of schedule. Additional patients continue to be enrolled and treated on several arms of NCI-MATCH that remain open.

Results of the Screening Phase

• Demonstrated feasibility of screening large numbers of patients at numerous accruing sites
  • 6,391 patient referrals were received
  • 5,954 patients’ biopsy samples were received and analyzed
  • 93% of the biopsies underwent successful molecular profiling
  • 37.6% of biopsies had an actionable mutation (i.e., matched a study arm)
  • 17.8% of patients were assigned to a study arm (26.4% if all arms were available simultaneously)
• Actionable mutation rates differed among tumor types
  • > 25% of patients with cholangiocarcinoma, melanoma, and cancers of the prostate, uterus, gastroesophageal junction, urothelium, central nervous system, or cervix matched
  • 5.8% of patients with pancreatic cancer matched

Each patient enrolled on NCI-MATCH contributes important information that may be useful in the design of better cancer treatments in the future.

Since co-occurring resistance mutations were common (71.3%) during the initial screening phase of the trial, combination targeted therapies could be an effective therapeutic approach for some patients. Plans are now underway to develop NCI-ComboMATCH, the first successor trial of NCI-MATCH, which will concentrate on targeted agents in combination treatments in signal-finding studies that are supported by preclinical in vivo evidence.

NCI-MATCH is being led by ECOG-ACRIN Cancer Research Group , part of NCTN, and DCTD’s Cancer Diagnosis Program with assistance from several other DCTD Programs.