- |||||||||| Journal: Cerebral Metastasis of a Gastrointestinal Stromal Tumor: A Case Report and Literature Review. (Pubmed Central) - Jul 14, 2025
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.
- |||||||||| Qinlock (ripretinib) / Ono Pharma, Stivarga (regorafenib) / Bayer, Ayvakit (avapritinib) / Blueprint Medicines
Review, Journal: Gastrointestinal Stromal Tumor: Current Approaches and Future Directions in the Treatment of Advanced Disease. (Pubmed Central) - Jul 2, 2025 In addition, this review emphasizes individualized treatment strategies within multidisciplinary expert teams, including surgery and other locoregional therapies, together with the importance of mutation-guided approaches, particularly for wild-type GISTs. Finally, it explores the potential of next-generation KIT inhibitors, combination therapies, and other investigational approaches.
- |||||||||| Romvimza (vimseltinib) / Ono Pharma
Review, Journal: Vimseltinib: First Approval. (Pubmed Central) - Jun 24, 2025 Vimseltinib received its first approval in February 2025 in the USA for the treatment of TGCT and is under development for the treatment of chronic graft versus host disease. This article summarizes the milestones in the development of vimseltinib leading to this first approval for the treatment of adult patients with symptomatic TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity.
- |||||||||| Journal: New treatments for systemic mastocytosis in 2025. (Pubmed Central) - Jun 5, 2025
Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results.
- |||||||||| Review, Journal: Medical Management of Tenosynovial Giant Cell Tumor. (Pubmed Central) - May 20, 2025
For an alternative to surgery, the CSF1R inhibitors pexidartinib and vimseltinib are approved in the United States for TGCT, and other CSF1R inhibitors are in clinical development...The potential risks and benefits of available treatments should be carefully considered in collaboration with a bone tumor-experienced, multidisciplinary team to determine the best course of care. Increased D-TGCT awareness and support through patient advocacy groups have helped to reshape the patient journey.
- |||||||||| Bavencio (avelumab) / EMD Serono, Romvimza (vimseltinib) / Ono Pharma
Trial completion date, Trial primary completion date: Study of DCC-3014 in Combination With Avelumab in Patients With Advanced or Metastatic Sarcomas (clinicaltrials.gov) - Apr 25, 2025 P1, N=32, Active, not recruiting, This case report may present the effectiveness of Ripretinib and introduce a relatively novel approach to clinical treatment. Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2025 --> Jan 2026
- |||||||||| Qinlock (ripretinib) / Ono Pharma, Stivarga (regorafenib) / Bayer
Second-line treatment patterns and outcomes of advanced gastrointestinal stromal tumor: A real-world study. (Hall A - Posters and Exhibits; Poster Bd #: 9) - Apr 23, 2025 - Abstract #ASCO2025ASCO_2041; P Our preliminary results suggest that ripretinib may offer superior clinical benefits for patients with primary KIT exon 11 mutations after failure of imatinib first line treatment. Its favorable safety profile and improved tumor response rate facilitated a higher rate of surgical intervention compared to sunitinib.
- |||||||||| Qinlock (ripretinib) / Ono Pharma, Stivarga (regorafenib) / Bayer
Optimizing second-line therapy for advanced gastrointestinal stromal tumors: Real-world efficacy and safety analysis (Villa Ciani) - Apr 3, 2025 - Abstract #SarcomaRC2025SARCOMA_RC_258; P Median PFS (mPFS) for ripretinib, sunitinib and regorafenib was 11.4, 12.4 and 2.8 months, respectively (p=0.296)...Conclusions Our preliminary results suggest that ripretinib may offer superior clinical benefits for patients with primary KIT exon 11 mutations after failure of imatinib first-line treatment...Editorial acknowledgement Legal entity responsible for the study The authors. Funding Has not received any funding.
- |||||||||| TGRX-3544 / Shenzhen TargetRx
TGRX-3544 is a highly potent and mutant-selective degrader of oncogenic KIT with oral activity (Section 18; Poster Board No: 16) - Mar 25, 2025 - Abstract #AACR2025AACR_4411; In summary, we have developed a highly mutant-selective, event-driven, scaffold-eliminating KIT degrader with superior cellular potency and in vivo oral activity. The balanced preclinical profile of TGRX-3544 supports its further clinical investigation in KIT-driven malignancies such as GIST and SM.
- |||||||||| Resistance to VEGFR inhibitors converges from molecular diversity in angiosarcoma cells (Section 11; Poster Board No: 18) - Mar 25, 2025 - Abstract #AACR2025AACR_3380;
However, therapeutic antibodies, such as bevacizumab (Avastin), and chemical inhibitors targeting VEGF pathways have shown limited clinical benefits in angiosarcomas...Then, we examined cellular response to VEGFR2 (Regorafenib, Sorafenib) and Tie2 inhibitors (Rebastinib, Pexmetinib) using cell growth inhibition assays...Furthermore, our results suggest angiosarcoma cells establish a functional convergence that potentiates the signaling activation of VEGF and Tie2 pathways, despite their molecular divergence. Our ongoing work aims to explore the molecular mechanisms promoting resistance to VEGF and Tie2 inhibitors.
- |||||||||| Qinlock (ripretinib) / Ono Pharma
Ripretinib Induced FSGS And Successful Treatment With Prednisone () - Mar 13, 2025 - Abstract #NKFSCM2025NKF_SCM_695; Overexpression of c-mip due to TKI causes disorders such as podocyte dysregulation and promotion of apoptosis, which cause FSGS. We propose that steroids might be a treatment option in Ripretinib induced secondary FSGS.
- |||||||||| Romvimza (vimseltinib) / Ono Pharma
Review, Journal: An evaluation of vimseltinib for treatment of tenosynovial giant cell tumors. (Pubmed Central) - Feb 27, 2025 In the MOTION study, the use of vimseltinib in patients with advanced TGCT resulted in a high objective response rate, substantial benefit in reducing clinical symptoms (such as pain and stiffness), and a favorable safety profile. Vimseltinib represents a promising new therapeutic option for patients with unresectable TGCT and is currently awaiting regulatory review by the FDA and EMA.
- |||||||||| Review, Journal: Emerging treatments for sarcoma: from 2024 onward. (Pubmed Central) - Jan 28, 2025
While these strategies have demonstrated some success, the overall improvements in survival have often been modest, irrespective of the therapeutic modality. This underscores critical concerns regarding the true cost-benefit balance and the potential for adverse effects, particularly when evaluated over extended follow-up periods.
- |||||||||| Review, Journal: Novel Therapeutics in Soft Tissue Sarcoma. (Pubmed Central) - Jan 12, 2025
Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the ?-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with NTRK fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma...The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry to develop treatments with a strong biologic rationale.
- |||||||||| inlexisertib (DCC-3116) / Ono Pharma
Review, Journal: A patent review of UNC-51-like kinase 1/2 inhibitors (2019-present). (Pubmed Central) - Jan 3, 2025 Despite the great success of ULK1/2 inhibitors development, ULK1/2 inhibitors are ATP competitive inhibitors of aminopyrimidines currently, and most ULK1/2 inhibitors are still in the preclinical research stage, with only DCC-3116 entered clinical research. Therefore, developing highly selective ULK1/2 inhibitors with low side effects and high bioavailability remains a challenging and promising research direction.
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