American Thyroid Association
American Thyroid Association
October 08, 2018
2 min read

LOXO-292 induces durable benefit in RET-altered thyroid cancer

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

LOXO-292 appeared effective among heavily pretreated patients with RET-mutant medullary thyroid cancer or RET fusion-positive thyroid cancer, according to data presented at the Annual Meeting of the American Thyroid Association.

LOXO-292 (Loxo Oncology) is an oral and selective agent in clinical development for cancers that harbor abnormalities in the rearranged during transfection (RET) kinase.

Researchers originally presented results from the global phase 1/2 LIBRETTO-001 trial at the ASCO Annual Meeting; the current analysis includes additional follow-up data from 29 patients with RET-mutant medullary thyroid cancer and nine patients with RET fusion-positive thyroid cancer.

Patients were heavily pretreated, with a median of three prior systemic regimens.

After a median follow-up of 8.4 months, 94% of those with medullary thyroid cancer who responded to LOXO-292 (n = 17) remained on therapy.

All seven patients with RET fusion-positive thyroid cancer who responded remained on therapy at a median follow-up of 8.5 months.

Researchers observed a confirmed overall response rate of 56% (95% CI; 35-75) among those with RET-mutant medullary thyroid cancer and of 78% (95% CI; 40-97) among those with RET fusion-positive thyroid cancer.

“I am very pleased to present the latest LOXO-292 clinical data to colleagues at [American Thyroid Association], demonstrating the activity and safety profile of this promising new agent for RET-altered thyroid cancers,” Lori J. Wirth, MD, associate professor of medicine at Harvard Medical School and Massachusetts General Hospital, said in a company-issued press release. “In the months since ASCO [Annual Meeting] we continue to see encouraging early evidence that LOXO-292 has the potential to provide durable responses in heavily pretreated patients with RET-driven cancers, with a promising safety profile at the phase 2 dose of 160 mg [twice daily].

Researchers included 82 patients in the safety analysis. Most treatment-emergent adverse events were grade 1. They included diarrhea (15% grade 1; 7% grade 2; 1% grade 3), fatigue (9% grade 1; 13% grade 2), dry mouth (21% grade 1), constipation (17% grade 1; 2% grade 2), hypomagnesemia (12% grade 1; 1% grade 2), cough (11% grade 1; 1% grade 2), headache (10% grade 1; 1% grade 2; 1% grade 3) and nausea (9% grade 1; 4% grade 2). Four patients experienced treatment-related grade 3 adverse events, including tumor lysis syndrome, increased alanine aminotransferase/aspartate aminotransferase, diarrhea and thrombocytopenia.

RET has been a known oncogene in thyroid cancer for many years and I am hopeful that these LOXO-292 data can further increase the awareness of this important target and, with breakthrough therapy designation in hand, that the clinical program will quickly advance to reach our patients in need,” Wirth said in the release.


Wirth LJ, et al. Abstract Short Call Oral 6. Presented at: 88th Annual Meeting of the American Thyroid Association; Oct. 3-7, 2018; Washington, D.C.

Disclosure: HemOnc Today could not confirm the authors’ relevant financial disclosures at the time of publication.