Lilly Receives FDA Approval for Treatment of RET-Driven Lung and Thyroid Cancers

Eli Lilly and Company announced the U.S. Food and Drug Administration (FDA) approved Retevmo™ (selpercatinib, 40 mg & 80 mg capsules), the first therapy specifically indicated for the treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). Retevmo was approved under the FDA's Accelerated Approval regulations based on the LIBRETTO-001 Phase 1/2 trial's endpoints of objective response rate (ORR) and duration of response (DoR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Retevmo is a selective RET kinase inhibitor. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. Retevmo is an oral prescription medicine, 120 mg or 160 mg based on weight, taken twice daily until disease progression or unacceptable toxicity.

"In the clinical trial, 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," said Alexander Drilon, M.D., acting chief of early drug development at Memorial Sloan Kettering Cancer Center and lead investigator for LIBRETTO-001. "The approval of selpercatinib 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. I am pleased that patients with these RET-driven cancers have this newly approved option."

Retevmo was evaluated in the single-arm, multi-center Phase 1/2 LIBRETTO-001 trial, the largest trial (N=702) of patients with RET-driven cancers. The trial enrolled both treatment-naive patients and heavily pretreated patients with a variety of advanced solid tumors including RET fusion-positive NSCLC, RET-mutant MTC, RET fusion-positive thyroid cancer, and certain other solid tumors with RET alterations. Major efficacy outcomes were ORR and DoR, assessed by a blinded independent review committee. Prespecified secondary endpoints included central nervous system (CNS) ORR and CNS DoR.

Up to 50 percent of patients with RET fusion-positive NSCLCs can have tumors that metastasize to the brain.2 Among previously treated NSCLC patients with measurable brain metastases, 10 out of 11 patients observed intracranial responses (CNS ORR), with all 10 patients experiencing a CNS DoR of greater than or equal to six months.

In the LIBRETTO-001 trial, there was a five percent discontinuation rate due to adverse reactions (ARs). The most common ARs, including laboratory abnormalities, (≥25 percent) were increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema (swelling in the arms or legs), decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation. In addition, the most frequent serious AR (≥ 2 percent) was pneumonia.