The Food and Drug Administration (FDA) has granted accelerated approval to Retevmo™ (selpercatinib; Lilly), a selective RET (rearranged during transfection) kinase inhibitor, for the treatment of:
- Adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC);
- Adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy;
- Adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
The approval was based on data from the multicenter, open-label, multi-cohort phase 1/2 LIBRETTO-001 trial that assessed the safety, efficacy, and pharmacokinetics of selpercatinib in 702 patients with advanced solid tumors with RET alterations. Patients received selpercatinib 160mg orally twice daily until unacceptable toxicity or disease progression. The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR), as determined by a blinded independent review committee (BIRC) according to RECIST v1.1.
Among 105 adult patients with RET fusion-positive NSCLC previously treated with platinum chemotherapy, the ORR was 64% (95% CI, 54-73), with 81% of patients having responses lasting ≥6 months. Among 39 patients with treatment-naïve RET fusion-positive NSCLC, results showed an ORR of 85% (95% CI, 70-94); 58% of these patients had responses lasting ≥6 months.
“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, MD, acting chief of early drug development at Memorial Sloan Kettering Cancer Center and lead investigator for LIBRETTO-001.
Among 55 patients aged ≥12 years with advanced or metastatic RET-mutant MTC who were previously treated with cabozantinib or vandetanib, the ORR was 69% (95% CI, 55-81), with 76% of patients having responses lasting ≥6 months. Among 88 treatment-naïve patients with RET-mutant MTC, the ORR was 73% (95% CI, 62-82); 61% of patients had reponses lasting ≥6 months.
Among 19 patients aged ≥12 years with RET fusion-positive thyroid cancer who were radioactive iodine (RAI)-refractory and received prior systemic therapy, the ORR was 79% (95% CI, 54-94) with 87% of patients having responses lasting ≥6 months. Among 8 patients with RET fusion-positive thyroid cancer who were RAI-refractory and systemic therapy naïve, the ORR was 100% (95% CI, 63-100); 75% of patients had responses lasting ≥6 months.
With regard to safety, the most common adverse reactions, including laboratory abnormalities, (≥ 25%) observed with treatment included increased AST/ALT, increased glucose, decreased leukocytes, decreased albumin, decreased calcium, dry mouth, diarrhea, increased creatinine, increased alkaline phosphatase, hypertension, fatigue, edema, decreased platelets, increased total cholesterol, rash, decreased sodium, and constipation.
The FDA previously granted Priority Review, Breakthrough Therapy and Orphan Drug designations to Retevmo for these indications. The Company is currently enrolling patients in 2 confirmatory phase 3 trials (LIBRETTO-431 and LIBRETTO-531).
Retevmo will be supplied as 40mg and 80mg capsules and is expected to be available within a week. Patients should be selected for treatment with Retevmo based on the presence of a RET gene fusion (NSCLC or thyroid cancer) or specific RET gene mutation (MTC) in tumor specimens or plasma. In LIBRETTO-001, identification of a RET gene alteration was prospectively determined by local laboratories using either next generation sequencing, polymerase chain reaction, or fluorescence in situ hybridization. An FDA-approved test for the detection of RET gene fusions and RET gene mutations is currently not available.
For more information visit retevmo.com.