Cullgen (Shanghai), Inc. has initiated a first-in-human (FIH) Phase I/II clinical trial (NCT07394374) to evaluate CG001419, an investigational oral therapy for patients with locally advanced or metastatic solid tumors. The study will focus on malignancies harboring neurotrophic tyrosine receptor kinase (NTRK) gene abnormalities, including fusions, point mutations, and amplifications. Unlike traditional kinase inhibitors, CG001419 is designed as a protein degrader, a novel modality intended to address resistance mechanisms often encountered with first- and second-generation TRK inhibitors.
Trial specifics
The study is an open-label, multicenter trial structured into two primary phases: a dose-finding phase (Phase I) and an indication expansion phase (Phase II). CG001419 is administered orally in tablet form, with the protocol exploring both once-daily (QD) and twice-daily (BID) dosing regimens across multiple cohorts (e.g., 400 mg, 600 mg, and 800 mg QD).
Phase I (Dose Exploration): Focuses on determining the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D). While this phase does not strictly require NTRK gene abnormalities for enrollment, priority is given to patients with oncogenic NTRK/TRK alterations.
Phase II (Indication Expansion): Will enroll specific cohorts of patients with confirmed oncogenic NTRK fusions, mutations, or amplifications to evaluate preliminary antitumor efficacy.
The trial seeks to enroll adult patients who have failed standard therapies or for whom no standard treatment is suitable. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and adequate organ function.
The primary endpoints for the Phase I portion are the incidence of dose-limiting toxicities (DLTs) and the establishment of the safety and tolerability profile. For the Phase II portion, the focus shifts to efficacy, measured primarily by the Objective Response Rate (ORR) according to RECIST v1.1 criteria. Secondary endpoints include pharmacokinetics (PK), Duration of Response (DOR), and Progression-Free Survival (PFS). The study was posted in Q1 2026 and is currently recruiting participants at clinical sites in China. NCT07394374.
Scientific and industry context
CG001419 is developed using Cullgen’s proprietary targeted protein degradation (TPD) platform. While existing TRK inhibitors like larotrectinib and entrectinib have transformed the treatment of NTRK-fusion positive cancers, many patients eventually develop resistance through solvent-front mutations or gatekeeper mutations. The biological rationale for CG001419 lies in its ability to not just inhibit, but eliminate the TRK protein entirely via the ubiquitin-proteasome system. By degrading the target, the molecule may overcome resistance driven by kinase domain mutations that render traditional inhibitors ineffective. This “degrader” approach represents an evolution from occupancy-based inhibition to catalytic protein removal.
The initiation of this trial places CG001419 within a highly specialized segment of the precision oncology market. It joins a competitive landscape that includes established TRK inhibitors and next-generation candidates such as Bayer’s larotrectinib and Bristol Myers Squibb’s repotrectinib. However, Cullgen’s candidate is differentiated by its modality; while most competitors are small-molecule inhibitors, CG001419 is among the first NTRK-targeting degraders to reach clinical-stage development.
The successful transition of CG001419 into FIH trials adds to a growing field of “molecular glues” and PROTACs (Proteolysis Targeting Chimeras) that aim to expand the druggable genome and provide durable options for patients with refractory solid tumors.