InnoCare's Zurletrectinib Wins China Approval as Next-Generation TRK Inhibitor for NTRK Fusion-Positive Solid Tumors

PHARMACEUTICALS

InnoCare Wins China Approval for Next-Generation Cancer Drug, Challenging Established TRK Inhibitor Market

BEIJING — Beijing InnoCare Pharma Tech Co., Ltd. said Monday that China's drug regulator has approved its experimental cancer therapy zurletrectinib — marketed under the brand name Yinuoxin — for the treatment of adults and adolescents aged 12 and older with solid tumors harboring NTRK fusion genes, a rare but aggressive class of mutations that can drive tumors across virtually every tissue type.

The approval, granted by the National Medical Products Administration on Dec. 9, 2025, hands InnoCare a significant regulatory milestone and positions the drug as a potential successor to first-generation TRK inhibitors, which have faced growing concerns about acquired resistance.

NTRK fusion-positive tumors, while rare — appearing in less than 1% of most common cancers — are disproportionately dangerous. They tend to progress rapidly and offer patients limited therapeutic options once standard treatments fail. Zurletrectinib, also known by its development code ICP-723 (CAS: 2403703-30-8), is designed to overcome the resistance mutations that eventually undermine earlier drugs in the class.

"NTRK fusion-positive tumors often progress rapidly with limited treatment options. Zurletrectinib has demonstrated exceptional efficacy."

— Professor Zhang Yizhuo, Sun Yat-sen University Cancer Center

Strong Clinical Results

Registration clinical trial data showed an overall response rate of 89.1%, with a disease control rate of 96.4%. At 24 months, the progression-free survival rate stood at 77.4% and the overall survival rate at 90.8% — figures that analysts say could differentiate the drug in a competitive landscape.

The results were particularly striking in certain patient subgroups. Among adolescent patients, the overall response rate reached 100%, according to Professor Luo Zhiguo of Fudan University Shanghai Cancer Center. In patients with soft tissue sarcoma — one of the more common tumor types in the trial — the response rate was 89.5%, said Professor Wang Qiming of Henan Cancer Hospital.

For NTRK fusion-positive lung cancer patients, the drug delivered an 88.9% response rate. Thyroid cancer patients enrolled in the study saw a 100% response rate.

Brain Metastasis Control

Perhaps the most clinically distinctive finding was zurletrectinib's ability to cross the blood-brain barrier — a persistent challenge in treating NTRK-positive cancers, which frequently metastasize to the central nervous system.

The drug demonstrated an intracranial objective response rate of 100%, with a 12-month intracranial duration of response of 100%, indicating robust control of brain lesions.

"Zurletrectinib also showed exceptional efficacy in NTRK fusion-positive lung cancer patients, with an ORR of 88.9%. It also demonstrated remarkable brain-penetrant activity, with an intracranial ORR of 100% and a 12-month intracranial DOR of 100%, achieving powerful control of brain lesions."

— Professor Chen Libo, Shanghai Jiao Tong University Affiliated Sixth People's Hospital

In a larger adult trial (NCT05745623), among three patients with baseline brain metastases, two — or 66.7% — achieved intracranial objective response, consistent with the drug's favorable brain penetration profile.

Pediatric Data Adds Depth

Data from a separate pediatric and adolescent trial (NCT04685226) further bolstered the clinical picture. As of the Nov. 23, 2024 data cutoff, 18 patients — eight children with a median age of 5.0 years (range: 3–9) and 10 adolescents with a median age of 13.5 years (range: 12–15) — were enrolled. Six patients were TRK inhibitor-naive with centrally confirmed NTRK-positive status.

The investigator-reviewed confirmed objective response rate was 100% (95% CI: 54.1–100.0). All patients achieved partial response at their first tumor assessment and maintained response through the cutoff date. Median time to response was 1.0 month in adolescents (95% CI: 0.99–NE) and 0.9 months in children (95% CI: 0.89–NE).

Notably, one pediatric patient who had progressed on a first-generation TRK inhibitor achieved a complete response after switching to zurletrectinib — a finding that underscores the drug's potential as a salvage therapy in resistant cases.

Safety Profile

In the adult safety population of 229 patients, treatment-related adverse events were predominantly Grade 1 or 2. The most common treatment-related adverse events occurring in at least 20% of patients were anemia (28.4%), aspartate aminotransferase elevation (27.9%), and alanine aminotransferase elevation (25.8%).

Grade 3 or higher treatment-related adverse events occurring in at least 2% of patients included weight gain (3.5%) and dizziness (2.2%). No serious treatment-related adverse events occurred in more than 2% of subjects. Treatment-related adverse events led to dose interruption in 9.2% of patients, dose reduction in 3.9%, and discontinuation in 0.4%.

In the pediatric trial, the most common treatment-related adverse events were ALT elevation (n=8) and anemia (n=6), mostly Grade 1 or 2. No events required dose reduction or discontinuation, and no serious treatment-related adverse events were reported. Pharmacokinetic results showed that zurletrectinib exposure in children and adolescents was similar to that observed in adults at the recommended Phase 2 dose.

Adult Trial Landscape

In the larger adult trial (NCT05745623), a total of 229 adult patients were enrolled across two study sites as of the Nov. 23, 2024 cutoff. Among them, 49 TRK inhibitor-naive patients with 12 different solid tumor types were evaluable for efficacy. The distribution of NTRK fusion genes was NTRK1 at 53.1%, NTRK2 at 2.0%, and NTRK3 at 44.9%. The median age was 51.0 years (range: 18–77), and patients had received a median of two prior lines of systemic therapy, with ECOG performance status of 0–1.

With a median follow-up of 11.7 months, the investigator-reviewed confirmed objective response rate was 83.7% (95% CI: 70.3–92.7), with five patients (10.2%) achieving complete response. Both median duration of response and median progression-free survival had not been reached at the time of analysis. At 12 months, the duration of response rate was 92.0% and the progression-free survival rate was 90.5%.

Reference: EP3822276