ALK rearrangement

P1, N=5, Active, not recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

Managing ALK-RCC is challenging due to its rarity and limited treatment options. Targeted therapies directed at the ALK gene may have a role in patients with ALK-RCC.

Herein, we report a case of oncocytic IDC of the parotid gland harboring a STRN::ALK fusion, further expanding the molecular landscape of this tumor. Although this fusion has been previously reported in intercalated duct IDC, to our knowledge, this is the first report of this specific fusion in oncocytic IDC.

P3, N=878, Recruiting, AstraZeneca | Trial completion date: Mar 2030 --> Nov 2030 | Trial primary completion date: May 2029 --> Nov 2030

Then the patient was recommended ALK-TKIs treatment after detecting ALK rearrangement, and achieved complete response (CR) from a second-generation ALK-TKI inhibitor, iruplinalkib, after resistance to the first-generation inhibitor crizotinib. This is the first case of iruplinalkib achieved therapeutic success in uterine IMT, suggesting that a sequential ALK-TKIs with iruplinalkib could be an optimal targeted therapeutic strategy for ALK-rearranged IMTs.

ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib has significantly improved clinical outcomes in ALK-rearranged NSCLC patients. To overcome these resistance mechanisms, the development of novel therapeutic strategies are required. By integrating structural biology, mutation evolution patterns, and emerging therapeutic approaches, this review underscores the need for next-generation inhibitors to overcome resistance and improve long-term outcomes in patients with ALK-positive NSCLC.

This case aims to provide reference for the diagnosis and treatment of patients with primary pulmonary IMT complicated by PNP. However, the follow-up period was short and systemic immunosuppressive therapy was not administered; this should be regarded as a cautionary note rather than a therapeutic recommendation.

These observed frequencies should be interpreted as case-level implementation signals surfaced through routine CGP rather than assay superiority evidence, biological prevalence estimates, or treatment-benefit data. This nationwide, platform-aware benchmark supports practical interpretation of tumor-agnostic eligibility signals in routine CGP practice in Japan.

This multinational registry-based analysis highlights evolving global treatment patterns, supports newer TKIs' effectiveness, and identifies clinical and molecular factors associated with treatment duration.

P2, N=118, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Completed

These findings suggest that osimertinib crosses the placenta with a moderate tissue uptake, while alectinib and its metabolite M4 do not appear to be transferred to the fetus but accumulate significantly within the placental tissue. Further studies are needed to guide treatment selection for NSCLC in pregnant women.