On April 25, 2025,InnoCare Pharma announced that its new generation pan-TRK inhibitor zurletrectinib (ICP-723) has been granted priority review by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA), which accepted the New Drug Application (NDA) of zurletrectinib for the treatment of patients with advanced solid tumors harboring NTRK gene fusions recently. Priority review is one of the key policies introduced by the CDE to accelerate drug approval.
In the registrational trial for patients with NTRK fusion-positive solid tumors, zurletrectinib demonstrated outstanding efficacy with a good safety profile.
Dr. Jasmine Cui, the co-founder, chairwoman and CEO of InnoCare, said, “We are delighted that zurletrectinib has been granted priority review. Zurletrectinib has demonstrated outstanding efficacy and a favorable safety profile. We anticipate it will provide better treatment options for eligible patients with solid tumors earlier.”
Zurletrectinib is a pan-TRK inhibitor developed by InnoCare. British Journal of Cancer, part of leading science journal Nature, published a paper entitled “Zurletrectinib is a next-generation TRK inhibitor with strong intracranial activity against NTRK fusion-positive tumors with on-target resistance to first-generation agents”.
The paper pointed out that zurletrectinib displayed strong potency against TRKA, TRKB, and TRKC WT kinases, as well as acquired resistance mutations TRKA G595R and TRKA G667C. Zurletrectinib was more active than other FDA approved or clinically tested first generation (larotrectinib) and next-generation (selitrectinib and repotrectinib) TRK inhibitors against most TRK inhibitor resistance mutations. Similarly, zurletrectinib (1 mg/kg BID) inhibited tumor growth in xenograft models derived from NTRK fusion-positive cells at a dose 30 times lower when compared to selitrectinib.
The paper further demonstrated that, in a central nervous system (CNS) penetrant pharmacokinetic study in SD rats, zurletrectinib showed improved ability to penetrate the blood-brain barrier, reaching the brain more effectively than selitrectinib and repotrectinib. Zurletrectinib‘s increased brain penetration was also translated into improved antitumor activity. In an orthotopic mouse glioma xenograft model carrying the TRKA G598R/G670A resistance mutation, zurletrectinib (15 mg/kg) significantly improved the survival of mice harboring orthotopic NTRK fusion-positive, TRK-mutant gliomas (median survival = 41.5, 66.5, and 104 days for selitrectinib, repotrectinib, and zurletrectinib respectively; P < 0.05), showing superior efficacy compared to repotrectinib (15 mg/kg) and selitrectinib (30 mg/kg) (P=0.0384 and 0.0022, respectively), with an excellent safety profile.
NTRK fusion genes occur in various types of adult and pediatric tumors. In some rare tumors, such as salivary gland carcinoma, secretory breast cancer, and infantile fibrosarcoma, the incidence of NTRK gene fusion exceeds 90%. It is estimated that there are about 6,500 new cases of NTRK fusion-positive solid tumors are diagnosed in China each year. There are significant unmet clinical needs in this area due to lack of effective treatment options.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
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Post time: May-07-2025