FDA approves Eli Lilly's Retevmo as first therapy specifically for advanced RET-driven lung, thyroid cancers

Eli Lilly announced that the FDA approved Retevmo (selpercatinib) capsules to treat non-small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other types of thyroid cancers in patients whose tumours have an alteration in rearranged during transfection (RET) gene. The agency noted that Retevmo is the first therapy approved specifically for patients with cancer with the RET gene alterations.

Anne White, president of Lilly Oncology, remarked that "Retevmo entered clinical trials in May of 2017 and is now approved less than three years later, representing the most rapid timeline in the development of an oncology medicine with multiple indications."

Specifically, Retevmo, a selective RET kinase inhibitor formerly known as LOXO-292, is indicated for the treatment of adults with RET fusion-positive NSCLC, and the treatment of patients aged 12 years and older with advanced or metastatic RET-mutant MTC who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory.

Retevmo, which gained priority review in January by the FDA, was approved under the FDA's accelerated approval regulations based on the LIBRETTO-001 Phase I/II trial's endpoints of objective response rate (ORR) and duration of response (DoR). The 702-patient trial enrolled both treatment-naive patients and heavily pre-treated patients with a variety of advanced solid tumours including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumours with RET alterations. Patients received Retevmo orally twice daily until disease progression or unacceptable toxicity.

According to the FDA, efficacy for NSCLC was evaluated in 105 adults with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR was 64%. The agency noted that for 81% of patients who had a treatment response, their response lasted at least six months. In 39 patients with RET fusion-positive NSCLC who had never undergone treatment, the ORR was 84%. Further, for 58% of patients who had a treatment response, their response lasted at least six months. 

Efficacy for MTC was evaluated in 143 patients aged 12 years and older with RET-mutant MTC. Participants had advanced or metastatic RET-mutant MTC and 55 had been previously treated with cabozantinib, vandetanib or both, while 88 patients had not been previously treated with an approved therapy for MTC. The FDA indicated that the ORR for the previously treated patients was 69%. For 76% of patients who had a treatment response, their response lasted at least six months. In patients who had not been previously treated, the ORR was 73%. For 61% of individuals who had a treatment response, their response lasted at least six months. 

Meanwhile, efficacy for RET fusion-positive thyroid cancer was evaluated in patients aged 12 years and older. The study enrolled 19 patients who were radioactive iodine-refractory (RAI) and had received another prior systemic treatment, and eight patients who were RAI-refractory and had not received any additional therapy. The ORR for the 19 previously treated patients was 79%. For 87% of participants who had a treatment response, their response lasted at least six months. The ORR in patients who had not received therapy other than RAI was 100%. For 75% of participants who had a treatment response, their response lasted at least six months. 

Eli Lilly said that  in the LIBRETTO-001 trial, there was a 5% discontinuation rate due to adverse reactions, with the most frequent serious adverse reaction being pneumonia.

Alexander Drilon, lead investigator for LIBRETTO-001, said that "we observed that the majority of metastatic lung cancer patients experienced clinically meaningful responses when treated with selpercatinib, including responses in difficult-to-treat brain metastases." Drilon added that "the approval "marks an important milestone in the treatment of NSCLC, making RET-driven cancers now specifically targetable in the same manner as cancers with activating EGFR and ALK alterations, across all lines of therapy."

Two confirmatory Phase III trials, LIBRETTO-431 and LIBRETTO-531, are currently enrolling patients.

Lily gained Retevmo through its acquisition of Loxo Oncology last year for about $8 billion. In December, Eli Lilly announced that as part of an overhaul of its cancer R&D operations, a new unit will be formed by combining its existing Lilly Research Laboratories oncology organisation and Loxo Oncology. 

To read more Top Story articles, click here.