Abstract B080: Update on the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH/EAY131) precision medicine trial
Authors: Harris Lyndsay , Chen Alice , O'Dwyer Peter , Flaherty Keith , Hamilton Stanley , McShane Lisa , Gray Robert , Li Shuli , Mitchell Edith , Dragaud Diane , Williams Mickey , Sklar Jeffrey , Iafrate A. John , Patton David , Little Richard F. , Zweibel James , Abrams Jeffrey , Doroshow James , Conley Barbara 
Published: August 2018

Purpose: NCI-Molecular Analysis for Therapy Choice (NCI-MATCH/EAY131), by ECOG-ACRIN (EA) and NCI, is the first national signal-finding trial to incorporate centralized NGS testing to direct patients (pts) to molecularly targeted parallel phase 2 treatment arms. We report status of accrual from opening on 08/12/15 thru 07/16/17 and future plans.

Methods: Eligible pts have advanced/refractory solid tumors, lymphoma, or myeloma. Drug treatments and molecular targets require stringent levels of evidence (LOE). Each arm (N-35) has a phase 2 dose, a molecular abnormality believed to predict response, and evidence of clinical activity. Pts must have enrolled by 05/22/17 with intent to submit fresh tissue or recent clinical biopsy. Tumor cores are shipped to the EA Central Biorepository & Pathology Facility at MD Anderson Cancer Center for evaluation of histopathology and % tumor; PTEN, MLH1, and MSH2 IHC; and RNA/DNA extraction. NGS is performed in one of 4 CLIA-accredited laboratories using the NCI-MATCH adapted Oncomine™ panel (Version 1.0; 143 genes with &gt;4000 reported variants including SNVs, indels, amplifications, and gene fusions). When an actionable mutation of interest (aMOI) or relevant IHC result is identified, the pt is assigned to treatment by a custom-designed informatics system (MATCHbox). If &gt;1 aMOI present, the pt is assigned by the variant with the highest LOE.

Results: As of 07/16/17, 5963 tumors were screened for 30 treatment arms. The assay success rate is 93%; median turnaround is 15 days (from sample receipt to return of results). 38.2% of pts have common cancers: colorectum (15.4%), breast (12.8%), lung (7.4%), and prostate (2.6%); 61.8% have less common tumors. The current overall match rate to aMOI’s is 18% (95% CI 17%, 19%); aMOI prevalence rates range from 3.47% to zero. The match rate also varies across tumor types: &lt;10% in pancreatic & SCLC; &gt;30% in bladder/urinary tract, uterine, and head/neck cancer. 998 pts have been assigned to Rx; 69% have enrolled. Of 30 arms, 8 have enrolled ≥ 35 pts; some arms with higher prevalence rates have been expanded to N=70 to accommodate pts with matching aMOIs. Arms with less frequent aMOIs will not complete accrual within the 6,000-pt central screening goal, leading to identification of pts for screening based on approved high-volume NGS labs’ assay results, verified centrally.

Conclusions: NCI-MATCH screened ~6000 pts at a rate that far exceeded expectations, and with acceptable toxicity; NGS was successful in 93%, well above the industry average of ~80%. The pace of enrollment, along with the trial’s availability at 1100+ sites, reflects the broad interest in the promise of genomics and the ability of such a trial to deliver on that promise. Lower accrual to "rare variant" arms led to use of high-volume NGS laboratories to complete the study. Follow-up will determine whether matching drugs to molecular targets results in meaningful response rates and improved patient outcome.

Citation Format: Lyndsay Harris, Alice Chen, Peter O'Dwyer, Keith Flaherty, Stanley Hamilton, Lisa McShane, Robert Gray, Shuli Li, Edith Mitchell, Diane Dragaud, Mickey Williams, Jeffrey Sklar, A. John Iafrate, David Patton, Richard F. Little, James Zweibel, Jeffrey Abrams, James Doroshow, Barbara Conley. Update on the NCI-Molecular Analysis for Therapy Choice (NCI-MATCH/EAY131) precision medicine trial [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B080.