NCI-MATCH Results Offer Clues for the Use of Agents Across Tumor Types

Jason Harris
Published: Friday, Feb 01, 2019
Lyndsay Harris, MD

Lyndsay Harris, MD

A trickle of positive findings from NCI-MATCH, a precision medicine trial of numerous agents across tumor types, has encouraged investigators to broaden the number of trial arms, which now stand at 40, and expand enrollment. Since the trial’s inception in 2015, molecular testing has been conducted on the tumors of 6000 patients and many arms have already closed to enrollment. Investigators expect to report more findings soon.

The landmark clinical trial conducted by the National Cancer Institute (NCI) and the ECOG-ACRIN Cancer Research Group channels patients into treatment arms based on molecular abnor-malities rather than cancer types. The trial is designed to determine if targeted therapies aimed at specific gene mutations will be effective regardless of tumor type. Investigators have identified 143 genes associated with cancer, specifically targeting mutations that cannot be treated by a current FDA-approved agent. Each arm of NCI-MATCH is evaluating at least 1 agent for efficacy across numerous common and rare cancer types.

“There is definitely some encouraging activity in a couple of the arms and some interesting observations about potential groups of tumors that would respond to the treatment,” Lyndsay Harris, MD, NCI study chair and deputy director of the NCI’s Cancer Diagnosis Program, said in an interview. “There are a number of studies that are mature but [investigators are] still in the process of submitting abstracts or writing their manuscripts. We should hear soon about some additional data.”

Findings from the EAY 131-Y arm reported in November showed that the investigational AKT inhibitor capivasertib (AZD5363) demonstrated clinical activity in patients with AKT-mutated cancers, supporting the validity of tailoring treatment to this tumor gene.

Preliminary data from 3 other arms of the trial (I, Q, and W) were released at the 2018 American Society of Clinical Oncology Annual Meeting. The results were considered mixed, although strong enough to warrant further investigation. And data from Arm Z1D released at the 32nd Society for Immunotherapy of Cancer annual meeting in 2017showed that nivolumab (Opdivo) demonstrated promising activity in mismatch repair–deficient noncolorectal cancers (CRCs).

One unexpected success of the trial is that enrollment of patients with rare or uncommon cancers has exceeded the initial estimate: 62.5% of enrolled patients have tumors other than the 4 most common cancers (breast, colorectal, non–small cell lung, and prostate), as opposed to the 25% original target for recruitment.

In November, Kevin Kalinsky, MD, MS, an assistant professor of medicine at NewYork-Presbyterian Hospital/Columbia University Medical Center, presented data from the EAY 131-Y arm. Thirty-five patients with metastatic AKT-mutated tumors who previously received at least 3 previous lines of therapy were assigned to twice-daily oral capivasertib, in weekly cycles of 4 days with treatment and 3 days without. Eight (23%) patients had tumor reduction and 16 (46%) had stable disease (SD). An estimated 52% of patients were alive and had SD 6 months following treatment.1

“We determined in advance that if 16% of patients experienced this response from the treatment, it would be a signal to move the drug on to a larger trial,” Kalinsky said in a statement. “This is a positive finding in a trial with patients whose cancers continued to grow despite previous treatments.”

In results from Arm I, 65 patients with mutations in the PIK3CA gene were assigned to taselisib, a potent and selective PI3K inhibitor that has shown sensitivity against the PI3K-α mutant isoforms and enhanced activity in PIK3CA-mutant tumors and cell lines in previous preclinical and clinical studies. Eligible patients had solid tumors or lymphomas that had progressed after 1 prior line of prior therapy or for whom there was no approved standard therapy. Thirty-two percent of patients in the cohort had 3 prior treatments and 37% had ≥3.2

Investigators did not observe any objective responses and 55% of patients had SD. However, 24% (90% CI, 17%-37%) of patients had a 6-month progression-free survival (PFS). The median PFS was 3.5 months (90% CI, 2.6-4.1). Even patients with aggressive cancer types, including lung cancer and cholangiocarcinoma, demonstrated prolonged SD.

Ian E. Krop, MD, PhD, and colleagues could not identify a pattern of mutations or a combination of mutations that predicted outcome. They added that it is possible PIK3CA mutations may not be the major driver in the tumors analyzed. Nonetheless, the investigators concluded that the disease control results are strong enough to continue investigating taselisib in these disease types.

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