Lilly’s RET inhibitor Retevmo shows early promise in new cancer types

Eli Lilly has revealed new early-stage data for its RET inhibitor Retevmo in new cancer types, as the company looks beyond the drug’s approved lung and thyroid cancer indications.

The phase 1/2 LIBRETTO-001 trial – presented at the virtual American Association for Cancer Research (AACR) annual meeting – enrolled 32 patients with 12 unique RET fusion-positive advanced cancer types, including pancreatic, colon, breast and salivary cancer, with 62.5% having gastrointestinal tumours.

Across all 32 patients who received Retevmo (selpercatinib), the researchers observed a confirmed objective response rate (ORR) of 46%, with the median duration of response not yet reach with a follow-up of 13 months.

According to Lilly, responses were ongoing in 73% of responding patients in the study.

"We are excited to broaden the body of evidence for Retevmo in RET fusion-positive cancers beyond lung and thyroid tumours," said David Hyman, chief medical officer, oncology at Lilly.

"These encouraging outcomes, including in difficult-to-treat GI malignancies, support a growing body of evidence that RET fusions are potentially actionable in a wide range of tumour types. These findings further demonstrate the importance of broad tumour profiling in advanced cancers,” he added.

Hyman said that Lilly will discuss the new data in the broad range of cancer types with regulatory authorities this year.

In May, Lilly received approval for Retevmo from the US Food and Drug Administration (FDA) for the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC), advanced or metastatic RET-mutant medullary thyroid cancer and advanced or metastatic RET fusion-positive thyroid cancer.

The pharma giant picked up the oral RET inhibitor after acquiring Loxo Oncology for $8bn in January 2019.

Although RET activating fusions and mutations are only observed in a small number of cancer patients – around 1-2% in NSCLC and 10-20% in papillary thyroid cancer – they are thought to be key disease drivers.

By inhibiting RET, researchers have found that significant benefits can be achieved in patients with these specific mutations.

"While uncommon, RET fusions occur in a 'long tail' of solid tumours beyond lung and thyroid cancers, and these patients do not yet have an approved targeted therapy option to address the underlying genomic driver of their cancer," said Vivek Subbiah, associate professor in the Investigational Cancer Therapeutics Department and centre clinical medical director of the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center.

"These results demonstrate [Retevmo]'s potential for this patient population and reiterate the importance of broad-based genomic profiling to identify actionable oncogenic drivers, including RET fusions,” he added.