FDA Approves Ibtrozi for ROS1+ Advanced Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration had approved Ibtrozi (taletrectinib) for adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

The efficacy of the treatment was evaluated in those with locally advanced or metastatic ROS1-positive NSCLC who were enrolled onto two multicenter, single-arm, open-label trials: TRUST-I and TRUST-II.

Among treatment-naive patients, the overall response rate was 90% in TRUST-I and 85% in TRUST-II, with 72% and 63% of responders, respectively, experiencing a duration of response of at least 12 months. Among patients who had previously received a ROS1 tyrosine kinase inhibitor, the overall response rate was 52% in TRUST-I and 62% in TRUST-II, with 74% and 83% of responders, respectively, having a duration of response of at least 6 months.

The efficacy population included 157 patients (103 in TRUST-I and 54 in TRUST-II) who were naive to ROS1 tyrosine kinase inhibitors and 113 patients (66 in TRUST-I and 47 in TRUST-II) who had received one prior ROS1 tyrosine kinase inhibitor. Some patients may have received prior chemotherapy for advanced disease. The major efficacy outcomes were confirmed overall response rate and duration of response, assessed by blinded independent central review using RECIST version 1.1.

This application was reviewed through the FDA’s expedited programs for serious conditions, including priority review, breakthrough therapy designation and orphan drug designation. These programs help speed up the development and review of promising treatments for serious or rare diseases.

Safety Data and Additional Efficacy Findings

For patients with ROS1-positive non-small cell lung cancer who had not previously received a tyrosine kinase inhibitor, Ibtrozi was associated with a high rate of disease control—meaning the cancer either shrank or stopped growing — in 95% of response-evaluable patients. Most people responded within about six weeks. Among those who responded, the benefit lasted a median of more than 3.5 years, and more than half were still responding after three years. At the time of analysis, half of patients had gone nearly four years without cancer progression, and about two-thirds were still alive.

Patients who had been previously treated with a tyrosine kinase inhibitor also experienced disease control with Ibtrozi, though the benefit was shorter. In this group, nearly 88% had stable disease or better. The median duration of response was almost 17 months, and just over 60% of patients were still responding after one year. Median progression-free survival in this group was nearly 10 months, and 78% were alive after one year.

Taletrectinib also showed activity in patients with measurable brain metastases, which are difficult to treat. Among tyrosine kinase inhibitor-pretreated patients with brain involvement, nearly two-thirds had their tumors shrink, and nearly all had disease control in the brain. These responses lasted a median of about 12 months.

Safety Overview

The safety of taletrectinib was evaluated in more than 350 patients who received the medication once daily. The most common side effects included elevated liver enzymes, diarrhea, nausea, and vomiting. About 1 in 5 patients experienced dizziness, while others reported taste changes or headaches. Side effects led to treatment being stopped in 7% of patients, though only 3% of these cases were thought to be directly related to the drug.

Most side effects were manageable, and many were similar to what patients might experience with other targeted therapies.

Prescribing Warnings and Recommended Dose

Ibtrozi may cause serious side effects, including liver problems, lung inflammation (pneumonitis), changes in heart rhythm (QTc prolongation), high uric acid levels (hyperuricemia), muscle pain with muscle damage, bone fractures and harm to an unborn baby. Patients should talk with their care team about these risks before starting treatment.

The recommended dose is 600 milligrams taken by mouth once daily on an empty stomach. Patients should avoid eating for at least two hours before and after each dose. Treatment continues until the cancer worsens or side effects require stopping or adjusting the dose.

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