Selpercatinib, a first-in-class highly selective RET kinase inhibitor, has been shown to maintain robust antitumor activity in patients with varying RET fusion-positive solid tumor cancers, according to data presented at the 2022 ASCO Annual Meeting by Vivek Subbiah, MD, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, and colleagues.

“Selpercatinib…is approved in multiple countries for the treatment of lung and thyroid cancer with RET fusions and medullary thyroid cancer with RET mutations,” wrote Dr Subbiah et al, who sought to provide an update on the safety and efficacy of this treatment in more patients with RET fusion-positive solid tumors and with longer follow-up than previously documented.

A total of 45 patients (median age, 53 years) with locally advanced and/or metastatic RET fusion-positive solid tumors were included in the phase 1/2 LIBRETTO-001; these patients had 14 unique tumor types, including 12 with pancreatic, 10 with colon, and 2 with breast cancers. Of these patients, 41 had received prior systemic therapy.

All patients were given ≥1 doses of selpercatinib, and after dose escalation, patients in the study were given selpercatinib 160 mg twice daily (the recommended dose). Responses to treatment were assessed in accordance with RECIST 1.1.

The efficacy analysis set was comprised of patients who were enrolled in the study ≥6 months before the cut-off date of September 24, 2021, and those who achieved responses were required to undergo an additional ≥6 months of follow-up. Additional follow-up was not a necessity for non-responders.

The primary end point of the study was objective response rate (ORR) determined by independent review committee (IRC), and secondary end points included ORR determined by investigator, duration of response, progression-free survival, time-to-response, and safety.

Among 41 efficacy-evaluable patients, the confirmed ORR by IRC was 44% (95% CI, 29-60). Furthermore, the investigators observed clinical benefit in 63%, including 2 complete responses, 16 partial responses, and 8 cases of stable disease ≥16 weeks.

According to the findings, responses occurred across a variety of fusion partners, and the median time-to-response was 1.9 months by IRC. The median duration of response was 24.5 months (95% CI, 9.2-not evaluable), and as of a median follow-up of 14.9 months, 50% of these responses were ongoing.

In addition, the median progression-free survival by IRC was observed to be 13.2 months (95% CI, 7.4-26.2), with 34.1% of patients reported as alive and progression-free at 16.4 months.

When compared with the broader safety database, there were no new safety signals observed. There were, however, 3 grade 5 adverse events documented, but they were deemed unrelated to treatment. A total of 4 patients discontinued treatment because of adverse events, 1 of which was related to treatment.

“Selpercatinib continued to demonstrate durable antitumor activity in patients with RET fusion-positive cancers across multiple tumor types,” Dr Subbiah and co-investigators wrote.

“These results emphasize the importance of comprehensive genomic profiling to identify actionable oncogenic drivers, including RET fusions,” they concluded.

Patients are still being enrolled in the LIBRETTO-001 trial.

Source:

Subbiah V, Wolf J, Konda B, et al. Tumor agnostic efficacy of selpercatinib in patients with RET fusion+ solid tumors: A global, multicenter, registrational trial update (LIBRETTO-001). Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 3094.