China’s NMPA has granted marketing approval to eratrectinib (VC004), a next-generation TRK inhibitor developed by Nanjing-based Jiangsu Vcare PharmaTech Co., Ltd., for adult and adolescent patients with advanced solid tumors harboring NTRK gene fusions. The tumor-agnostic approval is notable for extending coverage to patients who have progressed on first-generation TRK inhibitors — a population for whom treatment options remain limited — and represents the first domestically developed next-generation TRK inhibitor to reach the Chinese market.
Eratrectinib is an oral small-molecule inhibitor that targets the kinase domains of TRKA, TRKB, and TRKC, the proteins encoded by the NTRK1, NTRK2, and NTRK3 genes respectively. Unlike first-generation agents, which feature linear molecular scaffolds susceptible to solvent-front resistance mutations, eratrectinib employs a cyclic molecular structure designed to maintain binding affinity against common acquired resistance mutations while reducing off-target activity.
The approval was supported by a Phase II registration study in patients with NTRK fusion-positive solid tumors. In the overall population, eratrectinib demonstrated an objective response rate (ORR) of 68.5% and a disease control rate (DCR) of 85.2%. Among patients with at least six months of follow-up, the ORR reached 89.7% and the DCR was 100%, with a median overall survival of 40.7 months. The two-year progression-free survival rate was 75.7% and the two-year duration of response rate was 85.5%. In patients with baseline brain metastases, the ORR was 87.5%; in those previously treated with TRK tyrosine kinase inhibitors, the ORR was 47.4%. No specific trial identifier was provided in the company’s disclosure.
The cyclic scaffold distinguishes eratrectinib from larotrectinib (Vitrakvi), Bayer’s first-generation pan-TRK inhibitor approved by the US FDA in 2018, whose label excludes patients with known acquired resistance mutations. The structural approach is more analogous to that of repotrectinib (Augtyro), Bristol Myers Squibb’s macrocyclic next-generation ROS1/TRK inhibitor that received US FDA accelerated approval in June 2024 for NTRK fusion-positive solid tumors including patients with prior TRK-TKI exposure. The approval for eratrectinib – independently developed by Vcare and unpartnered based on publicly disclosed information – positions Vcare to address the post-first-generation-TKI segment within China, where an estimated 15,000 new NTRK fusion-positive solid tumor cases are diagnosed annually.
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