Lilly Announces Positive Registrational Trial Results for RET Inhibitor Selpercatinib in RET-Altered Thyroid Cancers, Plans NDA Submission by Year-End

Today, Eli Lilly and Company (Lilly) announced positive results from clinical trials of its RET inhibitor selpercatinib (LOXO-292) in patients with RET-altered thyroid cancer at the ESMO Congress. These results will support the company’s submission of a New Drug Application (NDA) to the FDA before the end of the year.

RET gene alterations include gene fusions and activating point mutations, which can lead to hyperactivation of the RET signaling pathway and uncontrolled cell growth. RET gene fusions occur in 2% of non-small cell lung cancer (NSCLC) cases, 10–20% of thyroid cancers, and a small number of other cancer types. Activating RET point mutations are found in 60% of patients with medullary thyroid cancer (MTC). Cancers harboring RET gene alterations primarily rely on the abnormal activation of this protein kinase to drive their proliferation and growth; therefore, these cancers are highly sensitive to RET inhibitors.

Selpercatinib is a highly selective and potent oral RET inhibitor acquired by Eli Lilly and Company through its acquisition of LOXO Oncology. It not only inhibits the native RET signaling pathway but also suppresses potential acquired resistance mechanisms. It has been granted Breakthrough Therapy Designation by the FDA for the treatment of patients with non-small cell lung cancer (NSCLC) harboring RET gene fusions, patients with medullary thyroid cancer (MTC) harboring activating RET mutations, and patients with advanced thyroid cancer harboring RET gene fusions.

Image source: Eli Lilly and Company official website

Data presented at the World Conference on Lung Cancer in early September showed that this precision therapy achieved an objective response rate of 68% in previously treated NSCLC patients. At the ESMO Congress, the company reported the efficacy of selpercatinib in patients with thyroid cancer and medullary thyroid cancer (MTC).

In patients with previously treated medullary thyroid cancer (MTC) harboring RET mutations, selpercatinib achieved an objective response rate (ORR) of 56%. Among this patient population, 53% had received prior treatment with more than two multikinase inhibitors (MKIs), including cabozantinib and vandetanib. The ORRs were highly similar regardless of whether patients had received prior MKI therapy. As of June 17 this year, the median duration of response (DOR) and progression-free survival (PFS) for these patients had not yet been reached.

In RET mutation-positive MTC patients who had not previously been treated with cabozantinib or vandetanib, selpercatinib achieved an ORR of 59%. The median DOR and PFS had not been reached, with the majority of patients still in response or progression-free survival.

In patients with RET fusion-positive thyroid cancer who had received multiple prior therapies, selpercatinib achieved an ORR of 62%. As the vast majority of patients remained in response or progression-free survival, the median DOR and PFS were also not yet reached.

“We are pleased that selpercatinib can provide meaningful improvements for patients with RET-altered thyroid cancer,” said Anne White, President of Lilly Oncology. “For decades, the RET gene has been established as an oncogenic driver in these cancers. These data demonstrate that selpercatinib is finally fulfilling our vision of achieving excellent clinical outcomes in both first-line and previously treated patients.”

References:

[1] Lilly Announces Positive Registrational Data for Selpercatinib (LOXO-292) in Heavily Pretreated RET-Altered Thyroid Cancers. Retrieved September 29, 2019, from https://investor.lilly.com/news-releases/news-release-details/lilly-announces-positive-registrational-data-selpercatinib-loxo

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