Taletrectinib For NTRK Fusion-Positive Solid Tumors Now Being Dosed in a Clinical Trial

The investigational next-generation tyrosine kinase inhibitor (TKI), taletrectinib (AB-106) has been dosed for the first time in a patient with an NTRK fusion-positive solid tumor being treated in a phase 2 study (NCT04617054), according to Innovent Biologics, Inc.

Taletrectinib’s mechanism of action allows it to target ROS1 and NTRK fusion mutations. ROS1 mutations occur in an estimated 2% to 3% of patients with advanced non–small cell lung cancer (NSCLC) and NTRK rearrangement is estimated to be a driver in approximately 0.5% of patients with other advanced solid tumors. The agent also has the potential to treat TKI-naïve or pretreated patients.

"Many patients with rare conditions, like NTRK fusion-positive cancer have limited treatment options and poor access to targeted therapies,” said Hui Zhou, PhD, senior vice president of clinical development at Innovent Biologics, in a press release. “We are very pleased to see that our partner AnHeart is advancing the phase II trial of taletrectinib in NTRK fusion driven solid tumors."

The phase 2 study has an estimated enrollment of 40 participants and an estimated completion date of December 2026. The primary outcome of the study is best overall response up to approximately 24 months. Secondary outcomes include duration of response, time to response, time to progression, intracranial best overall response, intracranial duration of intracranial response, progression-free survival, overall survival, adverse events, and plasma drug concentration.

In order to participate, patients must have a diagnosis of locally advanced or systemic metastatic solid tumors with a NTRK1/2/3 fusion gene, have failed or refused to accept the standard of treatment, have at least one measurable target tumor lesion, have an ECOG performance status of 2 or less, a minimum life expectancy of 3 months, adequate organ function, coagulation function, and any toxic effects caused by prior therapies must be recovered to Common Terminology Criteria for Adverse Events grade 1 or less, with the exception of alopecia.

Patients who have current participation in another clinical trial within 4 weeks before the first dose, prior treatment with an NTRK fusion gene and immune checkpoint inhibitors such as PD-1 and PD-L1, or symptomatic or unstable brain metastasis are not eligible for the study. Patients who have had major surgery or radiotherapy within 1 month before the first dose or are expected to need major surgery during the study, pneumonia caused by interstitial lung disease, interstitial fibrosis, or TKI, clinically active virial disease with positivity of serum human immune deficiency virus, hepatitis B virus, or hepatitis C virus, the systemic used of strong CYP3A inhibitors or inducers, any other anti-tumor drug within 14 days before the first dose or during the study, a history of neurological or mental disorder, or a historic drug use are also ineligible to participate.

The basket study was launched based on data from the ongoing phase 2 TRUST-II study (NCT04919811) of taletrectinib for the treatment of patients of NSCLC harboring with ROS1 fusion gene.

"Building upon the promising preliminary results in the Phase II trials for non-small cell lung cancer with ROS1fusions, we are moving forward with the Phase II trial of taletrectinib for NTRK fusion-driven solid tumors," said Bing Yan, MD, co-founde, and chief medical officer of AnHeart, in a press release. "We plan to enroll approximately 40 patients in this open-label, single-arm, multi-center phase II study in China."

REFERENCE:

Innovent announces first patient dosed in the phase II basket trial of taletrectinib for solid tumors with NTRK fusion. News release. Innovent Biologics. June 17, 2021. Accessed June 22, 2021. https://bit.ly/3xLauYa.