KIT exon 9 mutation

P3, N=482, Recruiting, Cogent Biosciences, Inc. | Active, not recruiting --> Recruiting

P2/3, N=255, Recruiting, Ningbo Newbay Technology Development Co., Ltd | Not yet recruiting --> Recruiting

P3, N=482, Active, not recruiting, Cogent Biosciences, Inc. | Trial completion date: Sep 2026 --> Jan 2030

Activating mutations in KIT or PDGFRA characterize most GISTs and confer sensitivity to imatinib, whereas succinate dehydrogenase (SDH)–deficient GISTs lack these mutations and are typically imatinib resistant...Pathology demonstrated spindle cell GIST with significant treatment effect and retained SDHB expression. This case suggests that oncogenic KIT signaling may remain the dominant driver of GIST behavior despite the presence of a germline SDHC mutation and highlights the importance of integrated molecular interpretation in GIST management.

Molecular testing identified a KIT Exon 9 mutation, leading to initiation of imatinib therapy...Multidisciplinary approaches combining imaging, histology, and molecular profiling are essential for optimizing outcomes in these complex cases. This extra-GI/pelvic GIST occurred under chronic posttransplant immunosuppression after renal and liver transplantation; as such, we highlight the transplant-oncology interface, notably, an elevated posttransplant cancer risk, rare but documented GIST after kidney transplant, and TKI-calcineurin-inhibitor interactions that require coordinated management.

P2/3, N=255, Not yet recruiting, Ningbo Newbay Technology Development Co., Ltd

Baseline body composition parameters, particularly myosteatosis, effectively predict the adverse events and DFS in patients taking imatinib. Personalized treatment, such as targeted nutritional and exercise interventions, and close monitoring of patients with myosteatosis or sarcopenia can enhance compliance and improve survival rates.

90Y-SIRT is a potent treatment for patients with liver metastases of GIST resistant to TKI therapy. In patients with 'q-wt' GIST, SIRT is an option for first-line use.

Molecular testing revealed a KIT exon 9 mutation and CDKN2A/B gene alterations, indicating aggressive tumor behavior and resistance to standard treatment. This case underscores the importance of recognizing atypical metastatic sites in GIST.

The SC formulation also significantly reduced tumor volumes and demonstrated dose-dependent histological responses, nearly eradicating tumor tissue in 11 days with the highest dose. These findings suggest that the SC slow-release formulation maintains stable drug concentrations during treatment, potentially improving therapeutic efficacy at the target site.

Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.

P2, N=23, Active, not recruiting, Asan Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024