Lilly and Bayer’s LOXO-195 shows efficacy in TRK inhibitor-resistant tumors at AACR

Among 29 patients, the drug – designed for patients who become resistant to TRK inhibitors like Vitrakvi – showed a 34 percent response rate, according to Phase I data.

dna, genomics

A drug intended for cancer patients whose disease becomes resistant to therapy targeting a rare genetic abnormality has shown potentially promising data at an ongoing oncology conference in Atlanta.

The American Association for Cancer Research said Monday that data for the drug, Eli Lilly subsidiary Loxo Oncology and Bayer’s LOXO-195 – now known as BAY 2731954 – showed 10 of the 29 patients evaluable for efficacy had a confirmed partial or complete response. All of the patients – 24 adults and seven children – had tumors that had acquired resistance to prior therapy with a TRK inhibitor, and BAY 2731954 is a TRK inhibitor designed to overcome that resistance. The data included 20 patients in an ongoing Phase I clinical trial and 11 who received BAY 2731954 through a Food and Drug Administration expanded-access protocol.

In November, Loxo and Bayer’s Vitrakvi (larotrectinib) received accelerated FDA approval for any solid tumor that exhibits an NTRK fusion. While NTRK fusions are very rare – accounting for about 0.5 percent of all cancers diagnosed in the US – targeting them has a high probability of producing a response. Indianapolis-based Lilly acquired Loxo in January for $8 billion.

“Unfortunately, most tumors that initially respond eventually become resistant to first-generation TRK inhibitors like larotrectinib,” Memorial Sloan Kettering Cancer Center chief of early drug development Dr. David Hyman said in a statement. “This is frequently because the tumor has acquired mutations in NTRK that reduce the ability of the therapeutic to block TRK activity.”

Another Loxo drug, LOXO-292, goes after a similar target known as a RET fusion, based on a similar premise to Vitrakvi. Data on that drug from a Phase I study presented at last year’s American Society of Clinical Oncology meeting in Chicago showed that LOXO-292 produced a 77 percent overall response rate, including 74 percent confirmed responses.

The first drug to win a tissue-agnostic label was Merck & Co.’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab), for MSI-H and dMMR cancers, but Vitrakvi was the first to win such a label as its sole approved indication. The rarity of the NTRK fusion-positive cancers, and their thin spread across different tumor types, means finding them will be akin to looking for a needle in a haystack. However, it could also spur the greater use of genomic sequencing in oncology.

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