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.

Among the tested compounds, entrectinib exhibited consistently strong binding affinities across all variants (-9.7 to -10.7 kcal/mol), whereas reduced binding affinities were observed for several inhibitors against E734K, A756D, and R897G variants...Clinical databases reported that p.Met918Thr (pathogenic) and p.Arg897Gln (risk factor) emerged as significant variants linked to MEN2-related cancers and Hirschsprung disease. As a conclusion, this integrative in silico study identifies deleterious RET nsSNPs with potential structural, functional, and therapeutic significance providing mechanisms for precision oncology and future clinical investigation.

P4, N=29, Not yet recruiting, Hunan Cancer Hospital

P=N/A, N=160, Not yet recruiting, Sun Yat-sen University

After an uneventful 5-day hospitalization without complications, the patient remains disease-free at the 12-month follow-up. This is the first report of neoadjuvant lorlatinib followed by uniportal VATS achieving pCR predicted by CMR in stage IIIB ALK-positive NSCLC, given the limitations of short-term follow-up and a single-case design.

P4, N=80, Not yet recruiting, Qiming Wang

P=N/A, N=35, Completed, Pfizer | Active, not recruiting --> Completed

Despite the lack of formal evidence for alternative formulations, pharmacokinetic data suggest adequate absorption. Crushed lorlatinib administered through a nasogastric tube represents a practical and effective option for dysphagic patients with ALK-positive NSCLC requiring early target-directed therapy.

The achievement of over 24 months of disease control underscores lorlatinib's potent activity against these complex molecular profiles. Our findings highlight the importance of recognizing and targeting rare ALK fusion variants-even when coexisting with other ALK rearrangements and resistance-associated mutations and expand the therapeutic landscape of precision oncology for advanced NSCLC.

This case supports studying the inclusion of newer ALK inhibitors in upfront therapy for pediatric ALK+ ALCL and supports the use of Lorlatinib to treat CNS relapse of ALK+ ALCL.

P2, N=9, Completed, University of Milano Bicocca | Recruiting --> Completed | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025