Elio Tissue Complete Assay Approved by FDA for Use in a Pembrolizumab-Based Trial

The FDA granted an Investigational Device Exemption approval to the Personal Genome Diagnostics Inc. elio<sup>TM</sup>&nbsp;tissue complete assay for use in a Merck trial evaluating pembrolizumab combinations in non&ndash;small cell lung cancer, according to a press release from PGDx, developer of the assay.

The FDA granted an Investigational Device Exemption (IDE) approval to the Personal Genome Diagnostics Inc. (PGDx) elioTMtissue complete assay for use in a Merck trial evaluating pembrolizumab (Keytruda) combinations in non—small cell lung cancer (NSCLC), according to a press release from PGDx, developer of the assay.1

The elioTMtissue complete assay will help in the identification of patients who are candidates for pembrolizumab-based combinations in the Merck trial, which will evaluate the efficacy of different pembrolizumab-based combinations based on the biomarker profile. Investigators hypothesize that this will help to better inform physicians in their future immunotherapy decisions.

“The IDE approval allows the PGDx elio tissue complete report to include mutation status forALK,ROS1,EGFR, andBRAF, in addition to TMB. This can enable faster trial accrual and increased patient enrollment,” John Simmons, PhD, vice president of Translational Medicine at PGDx toldTargeted Oncology. “This trial is an example of the assay’s value in investigating treatment strategies for cancer patients. This assay will be sued to analyze genomic markers to direct patient enrollment and stratification.”

This assay is a 500+ gene test that can be used to detect single nucleotide variants, small insertion/deletions, amplifications, rearrangements, microsatellite instability (MSI), and tumor mutational burden (TMB). The assay will determine genomic markers to determine patient enrollment and stratification in the trial.

According to an update on the KEYNOTE-495/KeyImPaCT trial at the European Society for Medical Oncology (ESMO), 288 patients were assigned to 1 of 4 groups based on biomarker screening. The groups included TMB-low/GEP-low, TMB-high/GEP-low, TMB-low/GEP-high, or TMB-high/GEP-high. Patients were then randomized to 1 of the 3 pembrolizumab combination regimens: pembrolizumab at 200 mg once every 3 weeks intravenously (IV) in combination with either anti-LAG-3 MK-4280 at 200 mg once every 3 weeks IV, lenvatinib (Lenvima) at 20 mg orally once daily, or CTLA-4 inhibitor MK-1308 at 25 mg once every 6 weeks IV for 35 cycles. Patients in the lenvatinib arm are allowed to receive lenvatinib monotherapy until disease progression or toxicity.2

The KEYNOTE-495/KeyImPaCT (NCT03516981) trial is a randomized, open-label, biomarker-directed phase II trial evaluating pembrolizumab-based therapy in patients with NSCLC. The trial is investigating the efficacy and safety of 3 pembrolizumab combinations in treatment-naïve patients with advanced NSCLC. The trial looks at 2 validated, independent next-generation biomarkers, which include T cell—inflamed gene expression profile and TMB.

“The trial is investigating the utility of biomarker-directed, pembrolizumab-based combination therapy for study participants with previously untreated advanced NSCLC,” said Simmons. “The PGDx elio tissue complete assay is being used during the enrollment process for the analysis of TMB status.”

Patients had to be at least 18 years old with either histologically or cytologically confirmed treatment-naïve advanced NSCLC. They had to have documented absence ofEGFRand BRAFmutations, and absence of ALK and ROS1 gene rearrangements, as well as measurable disease according to RECIST v1.1 criteria, and an ECOG performance status of 0 or 1.

Patients were excluded from the trial if they had significant cardiovascular impairment within 1 year of the first dose of the study drug, had symptomatic ascites or pleural effusion, or had had an allogenic tissue/solid organ transplant, among other exclusion criteria. The patients also could not have received prior systemic chemotherapy for metastatic or recurrent NSCLC, or have current NSCLC disease that can be treated with curative intent, either with surgery, localized radiotherapy, or chemoradiation.

Responses are assessed with RECIST v.1.1 by imaging in every 9 weeks for the first year, followed by every 12 weeks after that. The primary endpoint of the trial is investigator-assessed objective response rate. Secondary endpoints include progression-free survival, overall survival, and safety.

“Our ultimate goal is to bring this assay to market as an FDA cleared product, allowing local laboratories to perform comprehensive genomic profiling in-house, expanding patient access to precision medicine,” Simmons said.

Enrollment for this trial started in October 2018 and is still ongoing.


  1. Personal Genome Diagnostics Receives Investigational Device Exemption Approval from the FDA to Support Merck&rsquo;s Precision Oncology Trial. Business wire website. https://www.businesswire.com/news/home/20191204005228/en/Personal-Genome-Diagnostics-Receives-Investigational-Device-Exemption. Published December 4, 2019. Accessed December 4, 2019.
  2. Gutierrez M, Lam WS, Hellmann MD, et al. KEYNOTE-495/KeyImPaCT: A randomized, biomarker-directed, phase II trial of pembrolizumab-based therapy for non—small cell lung cancer (NSCLC),Annals of Oncology, Vol 30, Issue Supplement_5, October 2019, mdz260.111,https://doi.org/10.1093/annonc/mdz260.111