6:43 PM
Jun 08, 2018
 |  BioCentury  |  Product Development

Past not prologue

How luck and good timing factored into Loxo’s back-to-back home runs at ASCO

Loxo Oncology Inc.’s two-year streak of stunning data at ASCO appears to be the result of good decisions on the back of a healthy dose of luck. But it will be a tall order to make it a hat trick, given the third program is lined up more to meet a known need than break new ground.

Loxo’s first two programs came out of a 2013 partnership with Array BioPharma Inc., which yielded larotrectinib (LOXO-101) and LOXO-292, two compounds at the leading edge of a trend toward redefining cancers based on molecular profile rather than tissue of origin.

In both cases, Loxo benefited from good timing, coming on the heels of FDA discussions around tissue-agnostic drug development. The larotrectinib program, developed prior to the collaboration’s start, delivered a ready-made, first-in-class molecule against the neurotrophic tyrosine kinase receptor (Trk) -- a target Loxo was already eyeing.

“It was serendipitous with regards to the Array collaboration,” said CBO Jake Van Naarden. “It’s rare to have an emerging target paired with a purposely built drug that is a good inhibitor of that target. There was a little bit of luck there, that’s not usually how it goes.”

Larotrectinib is under Priority Review by FDA to treat any locally advanced or metastatic solid tumor that harbors a gene fusion involving Trk. The small molecule targets TrkA (NTKR1), TrkB (NTRK2) and TrkC (NTRK3). Its PDUFA date is Nov. 26.

Loxo is developing LOXO-292 for cancers with ret proto-oncogene (RET) alterations, and holds promise to be the first selective inhibitor of the kinase.

On June 2, Loxo reported updated data from a Phase I trial of LOXO-292 at the American Society of Clinical Oncology (ASCO) meeting. LOXO-292 produced a confirmed overall response rate (ORR) of 74% in 27 patients with RET fusion-positive non-small cell lung cancer (NSCLC), 71% in seven evaluable patients with RET fusion-positive thyroid or pancreatic cancer, and 33% in 18 evaluable patients with RET-mutant medullary thyroid cancer (MTC).

Twelve of the patients with RET fusion-positive cancers had CNS metastases at enrollment; all remain on study without...

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