Qinlock (ripretinib)

Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care.

P3, N=453, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Dec 2025 --> Dec 2026

P3, N=54, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Recruiting --> Active, not recruiting | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Feb 2026 --> Dec 2027

P=N/A, N=10, Completed, iOMEDICO AG | Recruiting --> Completed | N=100 --> 10 | Trial completion date: Nov 2027 --> Sep 2025 | Trial primary completion date: Sep 2027 --> Aug 2025

Cabozantinib enhances the radiosensitization of NSCLC cells through ferroptosis induction mediated by the suppression of the STAT3/MCL1/BECN1/SLC7A11 axis. These findings uncover a novel mechanism linking kinase inhibition to redox imbalance and suggest that the pharmacologic modulation of ferroptosis using multi-target TKIs may represent a rational approach to overcome radioresistance in NSCLC.

Results highlighted neurotoxicity as a significant concern for RTB and its metabolites, while metabolite 1 exhibited hepatotoxicity and nephrotoxicity. The current study unveils metabolic profiles of RTB and helps to understand the biotransformation products-related toxicity.

After initial surgery and adjuvant imatinib, the tumor recurred. Through comprehensive analysis of gene mutation profiles (KIT and HRR gene mutations, including BRCA2), a combination therapy of fluzoparib, pamiparib, and ripretinib was administered, stabilizing the patient's condition with significant efficacy. This case highlights the importance of genetic testing and personalized targeted treatment strategies for gastrointestinal stromal tumor (GIST) patients.

In advanced or metastatic disease, standard care involves sequential treatment with tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib. The expanding range of targeted therapies, such as avapritinib for the PDGFRA D842V mutation, underscores the importance of molecular profiling in guiding optimal treatment strategies. This review aims to summarize current knowledge on the diagnosis and treatment of GIST, with a focus on the role of molecular-genetic profiling, the therapeutic value of individual tyrosine kinase inhibitors, and emerging options for advanced disease, with particular emphasis on ripretinib.

Novel 4-anilinoquinoline and 4-anilinoquinazoline hybrids were designed and synthesized as PDGFR-α inhibitors based on lenvatinib, ripretinib and sorafenib. Furthermore, molecular docking results showed that 6o could stably bind to the ATP site of PDGFR-α rationalizing their potent anti-PDGFR-α activity. Based on the above findings, compound 6o could be considered an effective anti-angiogenesis candidate.

Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options, especially for rare GIST subtypes.

On the basis of the known safety profile of ripretinib, these increased ripretinib and combined ripretinib + DP-5439 exposures in participants with hepatic impairment are unlikely to be clinically relevant. Therefore, no dose adjustments are recommended for patients with gastrointestinal stromal tumor and hepatic impairment.

We report a case of a 58-year-old male with metastatic gastric GIST, treated with imatinib, followed by sunitinib and regorafenib, between October 2021 and December 2023, when he presented with sudden visual disturbances and a transient loss of consciousness...This case underscores the absence of effective systemic treatments for CNS disease, as most TKIs, including imatinib and ripretinib, have poor CNS penetration...This case highlights the need for novel therapeutic approaches targeting CNS metastases and further exploration of molecular mechanisms that enable atypical metastatic spread. This report contributes to the sparse literature on CNS involvement in GIST, emphasizing the need for a multidisciplinary approach and the development of therapies that can penetrate the blood-brain barrier (BBB) to improve outcomes in patients with advanced GIST.