FDA Approves Selpercatinib for Locally Advanced or Metastatic RET Fusion+ Solid Tumors

The FDA has granted accelerated approval to selpercatinib (Retevmo) for adult patients with locally advanced or metastatic solid tumors harboring a RET gene fusion that have progressed on or after previous systemic treatment or who have no satisfactory alternative treatment options.1

The regulatory decision was supported by data from the phase 1/2 LIBRETTO-001 trial (NCT03157128), which enrolled 41 patients with RET fusion–positive tumors other than non–small cell lung cancer and thyroid cancer.

RET fusions were detected in 97.6% of patients by leveraging next-generation sequencing, and 2.4% of these fusions were identified using FISH.

Selpercatinib elicited an overall response rate (ORR) of 44% (95% CI, 28%-60%) in the all-comer patient population, with 4.9% of patients achieving a complete response and 39% experiencing a partial response. The median duration of response (DOR) with the agent was 24.5 months (95% CI, 9.2–not evaluable), with 67% of patients experiencing a response that lasted for at least 6 months.

The tumor types that achieved responses were pancreatic adenocarcinoma, colorectal cancer (CRC), salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

In the 11 patients with pancreatic adenocarcinoma, the agent produced an ORR of 55% (95% CI, 23%-83%), with a DOR ranging from 2.5 months to 38.3+ months. In the 10 patients with CRC, the ORR with selpercatinib was 20% (95% CI, 2.5%-56%), with a DOR ranging from 5.6 months to 13.3 months. In those with salivary cancer (n = 4), the ORR was 50% (95% CI, 7%-93%), with a DOR ranging from 5.7 months to 28.8+ months. In the 3 patients with unknown primary cancer, the ORR with the agent was 33% (95% CI, 0.8%-91%), with a DOR of 9.2 months.

In the entire efficacy population, the median age was 50 years (range, 21-85) and 54% of patients were women. Moreover, 68% of patients were White, 24% were Asian, and 4.9% were Black. Seven percent of patients were Hispanic or Latino. Regarding ECOG performance status, 95% had a status of 0 or 1 and 5% had a status of 2. Most patients (95%) had metastatic disease. Ninety percent of patients received previous systemic treatment, with a median of 2 prior lines received (range, 0-9). Notably, 32% of patients received 3 or more prior lines of treatment.

Regarding safety, the most common adverse reactions experienced by at least 25% of patients included edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

References

1. FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. FDA. September 21, 2022. Accessed September 21, 2022. https://bit.ly/3f8Wzr7
2. Retevmo. Prescribing information. Eli Lilly and Company; 2022. Accessed September 21, 2022. https://bit.ly/3Sk1wvq