On 21 September 2022, the Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult patients with locally advanced or metastatic solid tumours with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

Efficacy was demonstrated in LIBRETTO-001 (NCT03157128), a multicentre, open-label, multi-cohort study that evaluated 41 patients with RET fusion-positive tumours (other than non-small cell lung cancer [NSCLC] and thyroid cancer) with disease progression on or following prior systemic treatment or who had no satisfactory alternative treatment options. The efficacy evaluation was supported by data in 343 patients with RET fusion-positive NSCLC and thyroid cancer enrolled in the same study already described in product labelling. Patients received selpercatinib until disease progression or unacceptable toxicity.

The primary efficacy measures were overall response rate (ORR) and duration of response (DoR) as determined by a Blinded Independent Review Committee. Among 41 evaluable patients, ORR was 44% (95% confidence interval [CI] 28, 60) with a DoR of 24.5 months (95% CI 9.2, not estimable). Tumour types with responses included pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

The median age of patients was 50 years (range, 21 to 85). Selected demographics were as follows: 54% female; 68% White, 24% Asian, 4.9% Black; 7% Hispanic/Latino; 95% had ECOG performance status of 0 or 1; 95% had metastatic disease. Thirty-seven patients (90%) received prior systemic therapy (median 2 [range, 0-9]; 32% received 3 or more). The most common cancers were pancreatic (27%), colorectal (24%), salivary (10%), and unknown primary (7%). RET fusion-positive status was detected in 97.6% of patients using NGS and 2.4% using FISH.

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 review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date. 

This application was granted accelerated approval based on ORR and DoR. Continued approval may be contingent upon verification of clinical benefit in confirmatory studies.

This application was granted priority review.

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.