Jiangsu Vcare's Next-Generation TRK Inhibitor Eratrectinib (VC004) Capsules, Have Been Included in Priority Review

　　Recently, Eratrectinib (VC004) capsules, a self-developed next-generation anti-resistant TRK inhibitor by Jiangsu Vcare PharmaTech Co., Ltd. (Jiangsu Vcare), were included in the priority review list by the NMPA, through public notice. This milestone positions the drug within the first tier of next-generation anti-resistant products targeting the same mechanism in China.

　　Eratrectinib capsules are intended for adult and adolescent patients (aged 12 years and above) with solid tumors meeting the following criteria: harboring a NTRK fusion gene; presenting with locally advanced or metastatic disease, or where surgical resection may cause severe complications; and having no satisfactory alternative treatment options or experiencing failure with prior therapy.

　　Adult Phase I clinical data for Eratrectinib capsules was prominently presented at the ASCO 2024: In patients naïve to TRK TKI treatment, the confirmed ORR in the RP2D expansion cohort was 73.1% [95% CI, 52.2-88.4]; Among 3 subjects who had progressed on prior TRK-TKI therapy, 2 achieved tumor shrinkage, with 1 achieving PR(39.6%); The vast majority of patients experienced rapid onset of efficacy and sustained long-term survival benefits following VC004 treatment, with the longest duration of response exceeding 36 months; Among 6 subjects with baseline brain metastases, intracranial lesions shrank by 61.8% and 25% in 2 subjects, respectively, while non-target lesions disappeared in 2 other patients after 4 months of treatment. Regarding safety, TRAEs were predominantly Grade 1-2, with no fatal TRAEs reported. Compared to other drugs in the same class, no new safety signals were identified.

　　About Eratrectinib

　　Eratrectinib (VC004) is a Class I small molecule targeted anti-tumor innovative drug independently developed by Jiangsu Vcare. As a next-generation TRK inhibitor, it has demonstrated superior efficacy compared to first-generation drugs targeting the same mechanism in clinical settings and addresses the issue of acquired resistance associated with first-generation drugs. It holds promise for delivering longer survival benefits and improved quality of life for patients. Currently, all first-generation drugs targeting this mechanism in the Chinese market are imported and have not yet received full marketing approval; furthermore, no second-generation drugs targeting this mechanism have been approved in China. This highlights the significant unmet clinical need. Eratrectinib possesses the following differentiated advantages:

　　1. Unique Second-Generation Anti-Resistance Mechanism: Based on in vitro kinase assay results, Eratrectinib not only exhibits comparable inhibitory activity against wild-type TRK to first-generation drugs in the same class but also demonstrates activity against first-generation drug resistance mechanisms. Its inhibitory potency against TRK mutant kinases reaches the nM level.

　　2. Significant Efficacy in Both Treatment-Naïve and Pre-Treated Patients: Based on results from the single-arm, pivotal Phase II clinical study, Eratrectinib demonstrated a higher clinical ORR than first-generation drugs. It also achieved favorable therapeutic outcomes in TRK TKIs pre-treated patients, further validating the differentiated advantages identified during the drug discovery phase in clinical studies.

　　3. Improved Clinical Safety Profile: The incidence of Grade ≥3 TRAEs was significantly lower compared to other drugs targeting the same mechanism, with no fatal TRAEs reported.

　　Eratrectinib is advancing in China through a single-arm Phase II trial as its pivotal clinical study, with an NDA submission imminent. Its IND application in the United States has already been approved, positioning it as a potential globally leading next-generation TRK inhibitor.

　　About NTRK Fusion-Positive Solid Tumors

　　NTRK gene fusions have been identified as oncogenic drivers in both adult and pediatric patients with a wide range of solid tumors. The NTRK genes (NTRK1, NTRK2, and NTRK3) encode the TRKA, TRKB, and TRKC receptors of the TRK family. These fusions act as drivers in multiple cancers and are found across numerous solid tumor types. Currently, NTRK fusion inhibitors show remarkable efficacy in the clinic, holding immense potential in the field of oncology. In China, NTRK gene fusion mutations are observed in prevalent cancer types such as lung cancer, colorectal cancer, breast cancer, and thyroid cancer, as well as in certain rare cancers, including secretory breast carcinoma and salivary gland secretory carcinoma.

Nat Rev Clin Oncol. 2018 Dec;15(12):731-747.