ViewPoints: WCLC - Loxo holds steady in RET, while EMSO awaits for larotrectinib

An incremental update from Loxo Oncology's non-small lung cancer candidate should still be enough to keep it on the right track- but doesn't do much to relieve the pressure on more advanced candidates.

What happened

Loxo presented updated data from its LIBRETTO-001 study of LOXO-292 on September 25, saying that 96 percent of non-small-cell lung cancer (NSCLC) patients have remained responsive since its last data cut-off presented at the American Society of Clinical Oncology (ASCO) meeting in June. (See ViewPoints: Loxo chalks up another ASCO win)

With the inclusion of eight new patients since the ASCO update, Loxo said that its overall response rate is now at 68 percent- a bit of a downtick from the 77 percent it had previously reported. Importantly, four of four patients with intracranial lesions had at least a partial response to the therapy, and one unconfirmed response reported at ASCO has now been confirmed.  The study's median follow-up is now 8.5 months, or 9.5 months among responding patients.

The trial is evaluating NSCLC patients with RET fusions, along with RET-mutant patients with medullary thyroid cancer (MTC). MTC response rates have been trending lower than NSCLC, but given the venue for Loxo's presentation- the World Conference on Lung Cancer- the company did not update performance in MTC. That data will be available next month at the American Thyroid Association meeting.

The bigger picture

With the latest data slice, things still look to be running smoothly for the LOXO-292 programme. Even with the drop-off in response rates from earlier this year, it is still comfortably ahead of a competing programme at Blueprint Medicines. While BLU-667 had generated excitement back in April with a 50-percent response rate in NSCLC patients with a RET mutation, Loxo's data released in June trounced much of that excitement. (See ViewPoints: Blueprint lays down a promising marker in RET duel)

On the other hand, sailing hasn't been quite as smooth recently for Loxo's lead candidate, larotrectinib. The company has waited longer between updates for the tropomyosin receptor kinase (TRK) inhibitor, with its last data cut off in July 2017, included in the New England Journal of Medicine publication. The next slice is expected next month at the European Society for Medical Oncology (ESMO) meeting, where investors will be eagerly watching to see if the candidate has maintained the high response rates it was observing across solid tumours with TRK fusions, as well as how long treatment durations are now stretching- and if the results can support a tissue-agonist approval. (See ViewPoints: Loxo Oncology builds case for being next in line for a genetically defined cancer approval

And while robust ESMO data may be sufficient to quell any investor uncertainty, a disclosure last week that there may not be as many TRK inhibitor-eligible patients as previously modelled has certainly increased pressure on the programme. That leaves two major overhangs for the company to work through- updated ESMO data, and results from a potential competitor in the form of entrectinib from Roche. The pharma said this week that it's planning an application for the candidate in ROS1-positive NSCLC, with plans to work further into the TRK population. (See ViewPoints: Loxo dinged by greater transparency)

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