FDA Approves Selpercatinib for Locally Advanced or Metastatic RET Fusion-Positive NSCLC and Solid Tumors

The Food and Drug Administration (FDA) granted approval to the kinase inhibitor selpercatinib to treat adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, and solid tumors with a RET gene fusion who have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

On May 8, 2020, selperactinib was granted accelerated approval for RET fusion-positive NSCLC based on initial results from the the multicenter, open-label, multi-cohort trial LIBRETTO-001 trial. This conversion to regular approval was granted based on data from additional patients, and follow-up data from the LIBRETTO-001 trial. Efficacy was demonstrated in 316 patients with locally advanced or metastatic RET fusion-positive NSCLC. Primary efficacy measures were overall response rate (ORR) and duration of response (DOR).

The ORR for treatment-naïve patients (n = 69) was 84% (95% confidence interval [CI], 73 to 92), and for patients previously treated with platinum-based chemotherapy (n = 247), it was 61% (95% CI, 55 to 67). The DOR of treatment naïve patients was 20.2 months(95%CI, 13 to not estimable [NE]), and for the platinum-exposed patients it was 28.6 months (95%CI, 20 to NE).

The LIBRETTO-001 trial also included cohorts of patients with RET fusion-positive solid tumors other than NSCLC or thyroid cancer who had progressed on or were intolerant to first-line therapy. This cohort received selpercatinib in oral dosages or either 120 mg or 160 mg twice daily based on body weight (less than 50 kg vs more than 50 kg, respectively) until disease progression or unacceptable toxicity, with primary efficacy measures of overall response rate (ORR) and duration of response (DOR).

Selpercatinib yielded an ORR of 44% (95% CI: 28 to 60) and a DOR of 24.5 months (95% CI: 9.2 to not estimable) in 41 evaluable patients.

Among responsive patients, 27% had pancreatic cancer, 24% had colorectal cancer, and 10% had salivary cancer. Other responsive tumor types included, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

The most common adverse reactions in both the NSCLC cohort and solid tumors cohort, occurring in ≥25% of patients, were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

Source:

FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer. United States Food and Drug Administration. September 21, 2022. Accessed September 22 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive-non-small-cell-lung

FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. United States Food and Drug Administration. September 21, 2022. Accessed September 22 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive-solid-tumors