Precision treatments aim to target cancers, based on specific genetic mutations or other factors.
Editor’s note: A version of this article originally appeared on the Frederick National Laboratory website.
NCI-MATCH, one of the largest cancer precision medicine clinical trials to date, closed in 2023 and its follow-on studies will use a similar model to test combinations of treatments, evaluating a patient’s immune system prior to pairing the patient with immunotherapy against their cancer.
The Molecular Analysis for Therapy Choice (NCI-MATCH) clinical trial was sponsored by the National Cancer Institute and ECOG-ACRIN Research Group, a membership-based network of academic and community-based cancer centers that designs and conducts clinical studies. NCI and ECOG-ACRIN are heading up the follow-on studies as well.
Through a fast, powerful type of genetic sequencing called next-generation sequencing combined with targeted treatment, NCI-MATCH aimed to determine whether certain cancer therapies could be used more broadly. If a medicine is effective against one type of cancer with a specific mutation, the trial asked, could it treat other cancers with the same mutation?
After the eight-year trial, scientists say an answer is coming into view: in short, yes. Medicines in seven of 27 arms of the trial showed the requisite level of broad effectiveness. The findings appear in Nature Medicine.
“The study met its goal as a signal-seeking endeavor, with a 25.9% average response rate in the published studies thus far,” Lyndsay Harris, M.D., associate director of NCI’s Cancer Diagnosis Program and a lead investigator on the trial, wrote in an email. “Perhaps most importantly we found that nearly two of five patients (38%) may have a candidate treatment revealed by [next-generation sequencing], which speaks to the value of this kind of testing in advanced cancer.”
While effectiveness in seven of 27 arms may appear modest, each arm encompassed many types of cancer and the participating patients’ cancers had already become resistant to many standard treatments. For some medicines to have been broadly effective amid those conditions is illuminating—and even the other negative results help crystallize scientists’ understanding of what works and what doesn’t.
“We learned a lot, and all of this is going to go into helping support the way future studies will be done with those drugs,” said Mickey Williams, Ph.D., director of the Molecular Characterization Laboratory at Frederick National Laboratory and an investigator on the trial.
An Open Door
The trial also determined that, in addition to the mutation that made them a target for the trial, many patients’ tumors had one or more genetic mutations that helped them resist various treatments.
“It opened the door to a lot of secondary and follow-up studies to continue,” Williams said.
Such efforts are already underway. The ComboMATCH trial launched in June. It’s like NCI-MATCH but will use combinations of medicines rather than single ones. Scientists hope to learn whether these will overcome the types of limitations and tumor resistance seen in NCI-MATCH.
iMATCH, which will identify key aspects of patients’ immune systems before pairing them with an immunotherapy against their cancer, has also begun. Another trial, MyeloMATCH, which will focus on biological markers in myelogenous cancers to assign patients to a targeted treatment, will launch later this year, indicated Harris.
While these could expand on NCI-MATCH’s findings, there are yet other learning opportunities to consider. NCI-MATCH revealed multiple areas for improvement.
These include planning new genetic sequencing trials with innovative, flexible designs that bring technologies to bear in new ways, said the investigators in the Nature Medicine report. Trials with a similar design to NCI-MATCH should include as many cancer targets and treatments as possible, maximizing the number of patients who can enroll. That increases the chances of helping people and makes the genetic sequencing results more powerful.
Another lesson underscored the need to enroll more patients from underrepresented populations. This is crucial for results to be broadly relevant to cancer patients of all backgrounds. NCI-MATCH reached and included patients at community hospitals, and future trials may be able to build on that foundation to better include these less-reached populations.
Technological Coming of Age
Next-generation sequencing and precision cancer treatment are much farther along than they were when NCI-MATCH began in 2015. In a sense, the two methods have proven themselves and come of age.
When the trial began, few people believed next-generation sequencing could be standardized between laboratories and used as it was in NCI-MATCH, Williams recalled. Precision medicine on this large scale was similarly a largely untapped opportunity surrounded by unanswered questions. The trial has swept away much of that uncertainty.
The Molecular Characterization Laboratory helped in this study by leading the next-generation sequencing consortium for the trial. They selected, validated, and collaborated to standardize the genetic sequencing assay used to screen patients’ tumor samples.
“Dr. Williams’ Molecular Characterization Laboratory was critical for the success of the NCI-MATCH trial, and he continues to be heavily involved in new precision medicine initiatives,” said Harris.
In doing so, the laboratory and the consortium have demonstrated that next-generation sequencing is viable for large clinical trials.
“We had people from all over that were so dedicated. It made me feel so good that we had an opportunity to play a role in this study,” Williams said.
Samuel Lopez leads the editorial team in Scientific Publications, Graphics & Media (SPGM). He writes for newsletters; informally serves as an institutional historian; and edits scientific manuscripts, corporate documents, and sundry other written media. SPGM is the creative services department and hub for editing, illustration, graphic design, formatting, multimedia, and training in these areas.