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The NCCN Clinical Practice Guidelines in Oncology for NSCLC recommend taletrectinib for the treatment of patients with advanced ROS1-positive NSCLC.
Non–Small Cell Lung Cancer |
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The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for Non-Small Cell Lung Cancers (NSCLC) have added taletrectinib (Ibtrozi) as a preferred agent for the first-line and subsequent treatment of patients with advanced ROS1-positive NSCLC.1,2
The guidelines also include recommendations for the use of taletrectinib—a highly selective, next-generation oral ROS1 TKI—in patients with brain metastases and resistance mutations. Specifically, taletrectinib is now listed as a preferred option in the first-line setting for the treatment of patients with ROS1 rearrangements discovered prior to the initiation of or during treatment with first-line systemic therapy.2 In the subsequent-line setting, the continuation of taletrectinib is listed as an option for patients with asymptomatic, symptomatic, or systemic disease with limited progression; the use of taletrectinib is recommended (if not previously given) for patients with asymptomatic, symptomatic, or systemic disease with multiple lesions; and taletrectinib was added as a preferred option for use in patients with symptomatic brain metastases. Furthermore, taletrectinib was added as an option for use in patients with resistant mutations like those in ROS1 G2032R.
“We are very pleased the NCCN acted with such urgency to review and update the NCCN Guidelines to include taletrectinib…as a preferred option for advanced ROS1-positive NSCLC across treatment lines, with particular recognition of benefit for patients with brain metastases and those with acquired resistance after first-line therapy,” David Hung, MD, founder, president and chief executive officer of Nuvation Bio, stated in a news release.1 “These updates address critical needs for patients across their treatment journeys, especially with the prevalence of central nervous system involvement for those living with ROS1-positive NSCLC. Additionally, this version builds further upon a previous guideline update that importantly highlights preferred utilization of ROS1-targeted agents instead of immunotherapy and chemotherapy for these patients.”
On June 11, 2025, the FDA approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC. The regulatory decision was supported by findings from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials.3 In the treatment-naive populations of TRUST-I (n = 103) and TRUST-II (n = 54), the respective overall response rates (ORRs) were 90% (95% CI, 83%-95%) and 85% (95% CI, 73%-93%). In total, 72% and 63% of responders in these respective populations had durations of response (DORs) lasting at least 12 months.
Among previously treated patients in these respective populations (TRUST-I, n = 66; TRUST-II, n = 47), the ORRs were 52% (95% CI, 39%-64%) and 62% (95% CI, 46%-75%). In total, 74% and 83% of responders in these respective populations had DORs lasting at least 6 months.
Notably, TRUST-I was an open-label, single-arm, nonrandomized study conducted in China that included 2 cohorts of patients with locally advanced or metastatic ROS1-positive NSCLC.4 Cohort 1 enrolled TKI-naive patients, and cohort 2 included patients who had progressed on crizotinib (Xalkori).
TRUST-II was a global, multicenter, open-label, single-arm, nonrandomized study that was also composed of 2 cohorts. Cohort 1 enrolled patients with TKI-naive, ROS1-positive NSCLC. Cohort 2 enrolled patients who had previously received 1 approved ROS1 TKI, either crizotinib or entrectinib (Rozlytrek).
A pooled analysis of TRUST-I and TRUST-II demonstrated that among TKI-naive patients with measurable brain metastases, the intracranial ORR (IC-ORR) with taletrectinib was 76.5% (95% CI, 50.1%-93.2%), and the intracranial disease control rate (IC-DCR) was 88.2% (95% CI, 63.6%-98.5%). At a median follow-up of 22.6 months, the intracranial DOR (IC-DOR) was 14.7 months (95% CI, 4.2-30.2). In TKI-pretreated patients with measurable baseline brain metastases, the IC-ORR was 65.6% (95% CI, 46.8%-81.4%), and the IC-DCR was 93.8% (95% CI, 79.2%-99.2%). At a median follow-up of 19.6 months, the IC-DOR was 11.9 months (95% CI, 6.9-23.5).
The prescribing information for taletrectinib includes precautions and warnings for hepatotoxicity, interstitial lung disease/pneumonitis, QTc interval prolongation, hyperuricemia, myalgia with creatine phosphokinase elevation, skeletal fractures, and embryo-fetal toxicity.3
The recommended dose of taletrectinib is 600 mg orally once a day on an empty stomach (defined as no food intake 2 or more hours before and 2 hours after taking taletrectinib) until disease progression or unacceptable toxicity.
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