Selpercatinib ( Retevmo ) is a highly selective and potent small molecule RET kinase inhibitor.
Researchers have reported an update on the efficacy and safety of Selpercatinib in RET-fusion+ non-small-cell lung cancer ( NSCLC ).
Patients with RET-fusion+ NSCLC were enrolled to the phase 1/2 LIBRETTO-001 trial, a global, multicenter trial ( 16 countries, 89 sites ).
Following the Phase 1 dose escalation portion of the trial, patients received the recommended dose of 160 mg orally twice daily. Each cycle was 28 days.
The primary endpoint was objective response rate ( ORR ) per RECIST 1.1. Secondary endpoints included duration of response ( DoR ) and safety.
Per health authority agreement, the primary analysis set was defined as the first 105 consecutively enrolled patients previously treated with Platinum-based chemotherapy.
Treatment-naïve patients were analyzed separately.
All analyses were based on a 16-Dec-2019 data cutoff date.
In the primary analysis set of Platinum-treated patients ( median of 3 prior systemic regimens; range 1-15 ), the ORR by investigator assessment was 70% ( 95% CI 59.8–78.1, n = 73/105 ).
Responses did not differ by fusion partner or number or type of prior therapies, including anti-PD-1/PD-L1 agents and off-label multikinase inhibitor use.
The median DoR was 20.3 months ( 95% CI 15.6–24.0 ) with 45 of 73 ( 62% ) responders censored at a median follow-up of 14.8 months.
Among 39 treatment-naïve patients, the ORR by investigator assessment was 90% ( 95% CI 75.8–97.1, n = 35/39, including 2 responses pending confirmation ).
Median DoR was not reached with 27 of 33 ( 82% ) confirmed responses ongoing at a median follow-up of 7.4 months.
In the safety analysis set consisting of all Selpercatinib dosed patients ( n=702 ), the most common treatment-related adverse events ( TRAEs ) that occurred in greater than or equal to 15% of patients were dry mouth ( 33.3% ), increased AST ( 24.5% ), increased ALT ( 23.8% ), hypertension ( 23.2% ), diarrhea ( 19.7% ), and fatigue ( 16.8% ).
Only 2% ( 14 of 702 ) of patients discontinued Selpercatinib for TRAEs.
In conclusion, Selpercatinib achieved marked and durable antitumor activity in patients with RET-fusion+ non-small-cell lung cancer.
Selpercatinib was well tolerated. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020