FDA Approves Selpercatinib for RET Fusion-Positive Non-Small Cell Lung Cancer and Locally Advanced or Metastatic Solid Tumors

FDA also approved the Oncomine Dx Target (ODxT) test as a companion diagnostic for selpercatinib.

Non-Small Cell Lung Cancer

Selpercatinib was granted accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-lung-and-thyroid-cancers-ret-gene-mutations-or-fusions) for its NSCLC indication on May 8, 2020, based on initial overall response rate (ORR) and duration of response (DOR) in 144 patients enrolled in the LIBRETTO-001 (NCT03157128) multicenter, open-label, multicohort trial. 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.

LIBRETTO-001 involved 316 patients who received selpercatinib until they experienced 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% 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).

Patients’ median age was 61 years (range = 23–92), and 58% were female. Their racial and ethnic groups were 49% White, 41% Asian, and 5% Black. Ninety-seven percent had ECOG performance status 0 or 1, and 97% had metastatic disease. Previously treated patients received a median of two prior systemic therapies (range = 1–15); 58% had received prior anti–PD 1/PD-L1 therapy.

Selpercatinib’s application for adult patients with locally advanced or metastatic NSCLC with a RET gene fusion was granted breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics). The application also was granted orphan drug designation.

Solid Tumors

The agent’s efficacy for locally advanced or metastatic RET fusion-positive solid tumors was demonstrated in LIBRETTO-001 (NCT03157128), a multicenter, open-label, multicohort trial that evaluated 41 patients with RET fusion-positive tumors (other than non-small cell lung cancer 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 or thyroid cancer enrolled in the same trial already described in product labeling. Patients received selpercatinib until they experienced disease progression or unacceptable toxicity.

The primary efficacy measures were ORR and DOR as determined by a blinded independent review committee. Among 41 evaluable patients, ORR was 44% (95% CI = 28, 60) with a DOR of 24.5 months (95% CI = 9.2, not estimable). Tumor types with responses included pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

Patients’ median age was 50 years (range = 21–85), and 54% were female. Their racial and ethnic groups were 68% White, 24% Asian, 5% Black, and 7% Hispanic/Latino. Ninety-five percent had ECOG performance status of 0 or 1, and 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 next-generation sequencing and 2.4% using fluorescence in situ hybridization.

Selpercatinib’s application for adult patients with locally advanced or metastatic solid tumors with a RET gene fusion used the Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. FDA granted accelerated approval based on ORR and DOR two months ahead of its goal date. Continued approval may be contingent on verification of clinical benefit in confirmatory trials. It was also granted priority review and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-serious-conditions-drugs-and-biologics).

The most common adverse reactions reported by at least 25% of adult patients in both clinical trials were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

The recommended selpercatinib dose based on patients’ body weight is:

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

View the full prescribing information for selpercatinib (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213246s008lbl.pdf).

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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).