FDA Grants Regular Approval to Selpercatinib for Locally Advanced or Metastatic RET+ NSCLC

The FDA has granted a regular approval to selpercatinib (Retevmo) for adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring a RET gene fusion, as detected by an FDA-approved test.1

In May 2020, the agent was previously granted an accelerated approval from the regulatory agency based on initial findings pertaining to overall response rate (ORR) and duration of response (DOR) in a total of 144 patients enrolled to the phase 1/2 LIBRETTO-001 trial (NCT03157128).2

The decision to convert the approval was supported by confirmatory data from an additional 172 patients and 18 months of additional follow-up to evaluate durability of response.

The multicenter, open-label, multicohort trial enrolled patients with advanced or metastatic RET fusion–positive NSCLC who had progressed on platinum-based chemotherapy and those with locally advanced or metastatic NSCLC without previous systemic therapy in separate cohorts.3

Participants received selpercatinib at a twice-daily dose of 160 mg until intolerable toxicity or progressive disease. Those who were included in the dose-escalation portion of the research were allowed to adjust their dose to 160 mg twice daily.

The major efficacy outcome measure of the trial was confirmed overall response rate (ORR) and duration of response (DOR) per blinded independent review committee and by RECIST 1.1 criteria.

In those who received prior platinum-based chemotherapy (n = 247), the median age was 61 years (range, 23-81), and 57% were women. Moreover, 44% of patients were White, 48% were Asian, 4.9% were Black, and 2.8% were Hispanic or Latino. Ninety-seven percent of patients had an ECOG performance status of 0 or 1 and 3% had a status of 2. The majority (97%) of patients had metastatic disease. Notably, patients had received a median of 2 previous systemic therapies (range, 1-15), with 58% of patients having previously received PD-1/PD-L1 therapy.

Ninety-four percent of patients had RET fusions detected using next-generation sequencing (NGS); 84.6% were detected via tumor samples, 9.3% were detected via blood or plasma samples, 4.0% were identified using FISH, 1.6% utilizing PCR, and 0.4% through other testing methods.

In these patients, the ORR achieved with selpercatinib was 61% (95% CI, 55%-67%), which included a complete response (CR) rate of 7.3% and a partial response (PR) rate of 54%. The median DOR in these patients was 28.6 months (95% CI, 20–not estimable [NE]), with 63% of patients experiencing a response that lasted for 12 months or longer.

In the 69 patients who were treatment naïve, the median age was 63 years (range, 23-92), and 62% were women. Moreover, 70% of patients were White, 19% were Asian, and 6% were Black. In this group, 94% had an ECOG performance status of 0 or 1, 6% had a status of 2, and 99% had metastatic disease. Ninety-one percent of patients had their RET fusion detected with NGS, 7.2% with FISH, and 1.4% using PCR.

In treatment-naïve patients, selpercatinib elicited an ORR of 84% (95% CI, 73%-92%), with a DOR of 20.2 months (95% CI, 13–not estimable [NE]), which comprised a CR rate of 5.8% and a PR rate of 78%. The median DOR in this group was 20.2 months (95% CI, 13-NE), with half of patients experiencing a response that lasted for at least 12 months.

Regarding safety, the most common toxicities 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 non-small cell lung cancer. News release. FDA. September 21, 2022. Accessed September 21, 2022. https://bit.ly/3DFyvq0
2. FDA approves first therapy for patients with lung and thyroid cancers with a certain genetic mutation or fusion. News release. FDA. May 8, 2020. Accessed September 21, 2022. https://bit.ly/3beo62M
3. Retevmo. Prescribing information. Eli Lilly and Company; 2022. Accessed September 21, 2022. https://bit.ly/3Sk1wvq