GIST Treatment Pipeline Shows Robust Activity with 28+ Therapies in Development Across Multiple Clinical Phases
Key Insights
DelveInsight's 2025 pipeline analysis reveals 25+ companies developing 28+ therapies for gastrointestinal stromal tumors, indicating strong industry investment in this rare cancer space.
Merck Sharp & Dohme initiated a belzutifan monotherapy study in August 2025 for advanced wild-type GIST (search) and other rare tumors, with objective response rate as the primary endpoint.
Key pipeline candidates include famitinib in Phase III development by Jiangsu Hengrui Medicine and novel approaches like Daiichi Sankyo's first-in-class GPR20 (search)-targeting ADC DS-6157.
The gastrointestinal stromal tumor (search) (GIST (search)) treatment landscape is experiencing significant expansion, with more than 25 companies actively developing 28+ pipeline therapies across various clinical stages, according to DelveInsight's comprehensive 2025 pipeline analysis.
Recent Clinical Trial Developments
On August 14, 2025, Merck Sharp & Dohme LLC initiated a pivotal study evaluating belzutifan monotherapy in patients with advanced or rare tumor types, including advanced wild-type gastrointestinal stromal tumor (search) (wt GIST (search)). The trial also encompasses pheochromocytoma (search)/paraganglioma (search) (PPGL), pancreatic neuroendocrine tumors (search) (pNET), von Hippel-Lindau (VHL) disease-associated tumors, and solid tumors with HIF-2α (search) related genetic alterations. The primary endpoint focuses on determining the objective response rate (ORR) of belzutifan, evaluated according to RECIST 1.1 criteria through blinded independent central review (BICR).
Additionally, Bayer announced on August 20, 2025, the initiation of a trial designed to evaluate BAY2927088 (sevabertinib (search)) in patients with HER2 (search)-mutated solid tumors, covering multiple cancer types including tumors of the colon, rectum, uterus, cervix, bladder, and biliary tract, though the trial specifically excludes individuals with advanced non-small cell lung cancer (search) (NSCLC).
Advanced-Stage Pipeline Candidates
Famitinib: Phase III Development
Jiangsu Hengrui Medicine is advancing famitinib, an orally active small molecule tyrosine kinase inhibitor, through Phase III clinical development for GIST (search) treatment. The drug targets multiple pathways including vascular endothelial growth factor receptor 2/3, platelet-derived growth factor receptor, and stem cell factor receptor (c-kit (search)). Famitinib is being developed against a wide variety of advanced-stage solid cancers, positioning it as a potentially significant addition to the GIST treatment arsenal.
Nilotinib: Repurposing for GIST
Novartis is investigating Tasigna (nilotinib hydrochloride monohydrate) in Phase II clinical trials for gastrointestinal stromal tumors. Originally indicated for chronic myelogenous leukemia (search) (CML), this orally available signal transduction inhibitor targets Bcr-Abl (search) kinase, c-kit (search), and Platelet Derived Growth Factor (PDGF), all of which play crucial roles in cell proliferation, migration, and angiogenesis.
Novel Therapeutic Approaches
THE-630: Addressing Resistance Mutations
Theseus Pharmaceuticals (search) is conducting Phase I/II studies of THE-630, a pan-variant inhibitor of the receptor tyrosine kinase KIT (search) designed specifically for patients with advanced GIST (search) whose cancer has developed resistance to earlier therapies. The drug addresses a critical unmet need, as mutations in the KIT protein can occur simultaneously in patients, leading to complex disease heterogeneity. In preclinical studies, THE-630 demonstrated potent in vitro and in vivo activity against all major classes of KIT activating and resistance mutations in GIST, achieving predicted pan-variant KIT inhibitory blood concentrations at tolerable doses with significant anti-tumor activity.
DS-6157: First-in-Class ADC Technology
Daiichi Sankyo Company is developing DS-6157, a potential first-in-class GPR20 (search) targeting antibody-drug conjugate (ADC) currently in Phase I clinical trials for GIST (search) treatment. This represents the fifth DXd ADC in Daiichi Sankyo's oncology pipeline to enter clinical development. The drug utilizes the company's proprietary DXd ADC technology, comprising a humanized anti-GPR20 monoclonal antibody attached to a novel topoisomerase I inhibitor payload via a tetrapeptide-based linker.
Industry Landscape and Therapeutic Diversity
The GIST (search) pipeline encompasses a diverse range of therapeutic modalities, including monoclonal antibodies, small molecules, peptides, polymers, and gene therapy approaches. Companies are pursuing various routes of administration including oral, parenteral, intravenous, subcutaneous, and topical delivery methods.
Leading pharmaceutical companies active in GIST (search) development include Jiangsu Hengrui Medicine, Daiichi Sankyo Company, Cogent Biosciences, Novartis, Bristol-Myers Squibb (search), GlaxoSmithKline, Takeda (search), and Theseus Pharmaceuticals (search), among others. The pipeline features promising therapies such as belzutifan, sunitinib, CGT9486, DCC-3116, ripretinib, and UCB4594.
The robust pipeline activity reflects the ongoing need for improved treatment options in GIST (search), particularly for patients who develop resistance to current standard-of-care therapies. The diversity of mechanisms of action and developmental stages suggests that patients may have access to multiple new treatment options in the coming years, potentially improving outcomes in this rare but challenging malignancy.