Promega to Develop MSI Technology as CDx to Merck’s Keytruda

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Promega said today it will develop its microsatellite instability (MSI) technology as an on-label, solid tumor companion diagnostic (CDx) to Merck’s blockbuster cancer immunotherapy Keytruda (pembrolizumab), through a global collaboration whose value was not disclosed.

Promega’s MSI testing is designed to functionally measure the genomic accumulation of insertion or deletion (INDEL) errors caused by a deficient mismatch-repair system (dMMR) that occurs in certain types of solid tumors. According to the company, such screening may be used to better characterize tumors and guide therapeutic choices for MSI-High cancer types.

Tumors with MSI-High status have been shown to respond to immune checkpoint inhibitor therapies—an outcome that Promega says may be explained by MSI-driven tumor expression of mutation-associated neoantigens (MANA) that are believed to cause immune cell infiltration into the tumor microenvironment. Tumor induced inhibition of immune cell activity can be overcome with ICI therapies, allowing for tumor cell destruction by the immune cells.

“Our test uses a sensitive and specific panel of markers for detection of MSI status and offers valuable insight to help inform physicians on how best to treat patients with cancer including those likely to benefit from immune checkpoint inhibitor treatment,” Jeff Bacher, Ph.D., senior research scientist, Promega, said in a statement.

Bacher added that unlike other DNA-based, molecular screening options, Promega MSI technology uses five monomorphic mononucleotides, reflecting a recommendation of the NIH’s National Cancer Institute. China’s National Medical Products Administration (NMPA) recently gave Promega’s MSI technology its innovation status and priority review.

The companies plan will initially seek regulatory approvals for the Promega MSI CDx in the U.S. and China, with possible plans to add approvals in additional areas of the world.

In February, Promega and collaboration partner FALCO biosystems of Kyoto, Japan, won CDx approval from Japan’s Ministry of Health, Labour, and Welfare for the MSI-IVD kit to identify patients suitable for treatment with Keytruda.

The kit—which incorporates Promega MSI chemistry and assay design—is intended to detect MSI-High within tumor tissues as a biomarker of DNA repair dysfunction, without corresponding submission of a blood sample, using multiplex PCR fragment analysis with Promega-designed five mononucleotide repeat markers, which have been shown to be less susceptible to genetic polymorphisms. The kit is the first pan-tumor companion diagnostic test in Japan, according to the companies.

Promega said today it intends to seek regulatory clearance for an MSI in vitro diagnostic (IVD) test in the U.S., as well as in China and Europe. The tests are intended to launch in the first half of 2020 in all three regions of the world.

Promega’s Research Use Only (RUO) MSI assay has been available and used in the market as part of Laboratory-Developed Tests since 2004.

In the U.S., the FDA approved the first CDx for Keytruda in 2015, when Agilent’s PD-L1 IHC 22C3 pharmDx assay was authorized as a companion diagnostic to the Merck immunotherapy, designed to detect PD-L1 expression in advanced non-small cell lung cancer (NSCLC).

NSCLC is one of five types of cancer for which the FDA has approved PD-L1 IHC 22C3 pharmDx as a CDx to Keytruda. Most recently in August, the Agilent assay was authorized as an aid in identifying patients with esophageal squamous cell carcinoma (ESCC). In between, the FDA approved the test for identifying patients with cervical cancer, gastric or GEJ adenocarcinoma, head and neck squamous cell carcinoma (HNSCC), and urothelial carcinoma.

On October 2, PD-L1 IHC 22C3 pharmDx was approved by NMPA as a companion diagnostic to identify patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 (tumor proportion score [TPS] ≥1%) for first-line treatment with Keytruda.

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