FDA Greenlights Companion Diagnostic for Selpercatinib in RET+ NSCLC and Thyroid Cancers

The FDA has approved the Oncomine Dx Target Test as a companion diagnostic to select patients with RET fusion–positive locally advanced or metastatic non–small cell lung cancer (NSCLC), advanced or metastatic thyroid cancer, and advanced or metastatic medullary thyroid cancer who could be candidates to receive selpercatinib (Retevmo).¹

With the next-generation sequencing (NGS)–based test, several alterations can be identified at once with a small sample size. With the assistance of the test, patients can be rapidly matched with an appropriate targeted therapy. The companion diagnostic has received regulatory approval in 17 countries for 15 targeted agents, according to Thermo Fisher Scientific.

“Following the Oncomine Dx Target Test’s first approval in 2017, we have worked to advance across to companion diagnostics for targeted therapies on a global scale,” Garret Hampton, president of clinical NGS and oncology at Thermo Fisher Scientific, stated in a press release. “As we continue to pursue additional approvals alongside our biopharma partners, we remain committed to broadening access to NGS-based testing to ensure patients and clinicians everywhere can benefit from it.”

Selpercatinib received accelerated approval from the FDA in May 2020 for use in patients with RET alteration–positive NSCLC, medullary thyroid cancer, and other thyroid cancers based on initial data on 144 patients enrolled to the phase 1/2 LIBRETTO-001 trial (NCT03157128).²

On September 21, 2022, the FDA converted the selpercatinib approval to a regular one for those with locally advanced or metastatic NSCLC harboring a RET gene fusion based on confirmatory findings from an additional 172 patients and 18 months of additional follow-up to examine durability of response.^3,4

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

Patients were given selpercatinib at 160 mg twice daily until unacceptable toxicity or disease progression. Primary outcome measures for the trial comprised confirmed overall response rate (ORR) and duration of response (DOR) by blinded independent review committee and in accordance with RECIST v1.1 criteria.

Among the subset of 247 patients who previously received platinum-based chemotherapy, the median age was 61 years (range, 23-81), and 57% were women. Additionally, 44% of patients were White, 48% were Asian, 4.9% were Black, and 2.8% were Hispanic or Latino. Regarding ECOG performance status, 97% had a status of 0 or 1 and 3% had a status of 2. Ninety-seven percent of patients had metastatic disease. Patients had received a median of 2 prior lines of systemic treatment, with a range of 1 to 15 therapies. More than half of patients (58%) received prior PD-1/PD-L1 therapy.

In this group, selpercatinib induced an ORR of 61% (95% CI, 55%-67%), with a complete response (CR) rate of 7.3% and a partial response (PR) rate of 54%). The median DOR was 28.6 months (95% CI, 20–not estimable [NE]), with 63% of patients having a response that continued for at least 1 year.

In the subset of 69 patients who did not receive previous treatment, the median age was 63 years (range, 23-92), 62% were women, and 70% were White. The ECOG performance status was 0 or 1 in 94% of patients, and 2 in 6% of patients. Almost all patients (99%) had metastatic disease.

Selpercatinib elicited an ORR of 84% (95% CI, 73%-92%) in these patients; the CR and PR rates were 5.8% and 78%, respectively. The median DOR was 20.2 months (95% CI, 13-NE), with 50% of patients experiencing a response that lasted for 12 months or longer.

The most common toxicities reported in this population were edema, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

In September 2022, selpercatinib received another accelerated approval for use in those with locally advanced or metastatic solid tumors harboring a RET fusion that have progressed on or after prior systemic treatment or who have no satisfactory alternative options. This decision was also based on findings from LIBRETTO-001.^5,4

In 41 patients with RET fusion–positive tumors other than NSCLC and thyroid cancer, the agent produced an ORR of 44% (95% CI, 28%-60%), which included a CR rate of 4.9% and a PR rate of 39%. In the all-comer population, the median DOR was 24.5 months (95% CI, 9.2-NE). Notably, 67% of patients experienced a response that lasted for 6 months or longer.

The tumor types that responded to selpercatinib included pancreatic adenocarcinoma (ORR, 55%; n = 11), colorectal cancer (ORR, 20%; n = 10), salivary cancer (50%; n = 4), unknown primary cancer (ORR, 33%; n = 3), breast cancer, soft tissue sarcoma, bronchial carcinoid cancer, ovarian cancer, cancer of the small intestine, and cholangiocarcinoma.

In this population, the most frequently experienced adverse effects included edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

References

1. Thermo Fisher Scientific announces FDA approval of Oncomine Dx target test as the first NGS-based companion diagnostic to aid in therapy selection for patients with RET mutations/fusions in thyroid cancers. News release. Thermo Fisher Scientific. September 27, 2022. Accessed September 29, 2022. https://bwnews.pr/3E3VtXT
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 29, 2022. https://bit.ly/3beo62M
3. FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer. News release. FDA. September 21, 2022. Accessed September 29, 2022. https://bit.ly/3DFyvq0
4. Retevmo. Prescribing information. Eli Lilly and Company; 2022. Accessed September 29, 2022. https://bit.ly/3Sk1wvq
5. FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. FDA. September 21, 2022. Accessed September 29, 2022. https://bit.ly/3f8Wzr7