On 21 September 2022, the US Food and Drug Administration (FDA) granted regular approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test.

FDA also approved the Oncomine Dx Target (ODxT) Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib.

Selpercatinib was previously granted accelerated approval for the NSCLC indication on 8 May 2020, based on initial overall response rate (ORR) and duration of response (DoR) in 144 patients enrolled in the LIBRETTO-001 (NCT03157128), a multicentre, open-label, multi-cohort study. The conversion to regular approval was based on data from an additional 172 patients and 18 months of additional follow-up to assess durability of response.

Efficacy was demonstrated in total of 316 patients with locally advanced or metastatic RET fusion-positive NSCLC. Patients received selpercatinib until disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DoR as determined by a Blinded Independent Review Committee. Among 69 treatment-naïve patients, ORR was 84% (95% confidence interval [CI] 73, 92) with a DoR of 20.2 months (95% CI 13, not estimable). Among 247 patients previously treated with platinum-based chemotherapy, ORR was 61% (95% CI 55, 67) with a DoR of 28.6 months (95% CI 20, not estimable).

The median age of patients was 61 years (range 23 to 92). Selected demographics were as follows: 58% female; 49% White, 41% Asian and 5% Black; 97% had ECOG performance status 0 or 1; 97% had metastatic disease. Previously treated patients received a median of two prior systemic therapies (range, 1 to 15); 58% had received prior anti PD1/PD-L1 therapy.

The most common adverse reactions (≥25%) in patients were oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

The recommended selpercatinib dose based on body weight is:

  • Less than 50 kg: 120 mg orally twice daily
  • 50 kg or greater: 160 mg orally twice daily

Full prescribing information for Retevmo is available here.

This application was granted breakthrough designation. The application also was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.