ROS1 fusion

P1, N=312, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

P2, N=56, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

One patient with acquired fusion gene mutations developed small-cell lung cancer transformation after ALK-TKIs resistance. Key Words: Lung cancer, ALK fusion, RET fusion, ROS1 fusion, EGFR-TKIs-resistance, Targeted therapy.

iza-bren demonstrated encouraging antitumor activity and a manageable safety profile in pretreated NSCLC patients with diverse GAs outside of classical EGFR mutations, especially in EGFR exon20ins/nonclassical and HER2 mutations.

The last follow-up in August 2025 showed the patient remained in good survival status. This case highlights a novel strategy of neoadjuvant targeted downstaging followed by surgical resection for small-lesion, highly invasive NSCLC, as well as the potential value of integrating postoperative Chinese-Western medicine management for long-term survival and treatment tolerance.

One case showed an NOL10::ALK out-of-frame fusion with negative ALK immunohistochemistry and equivocal ALK FISH results. Because the expression imbalance method can detect novel fusions, we recommend its implementation with confirmation testing.

The increase in HER3 expression induced by osimertinib treatment was associated with increased payload release in PC-9 cells. Our results indicate that HER3 dynamics, as well as baseline HER3 expression, modulate payload release from HER3-DXd and support combination strategies to potentiate the antitumor activity of HER3-DXd.

P=N/A, N=500, Not yet recruiting, The University of Sydney

The overall concordance of genotyping results between cfRNA-protected SS and paired CNB specimens was 100%, correctly identifying all ALK fusions, ROS1 rearrangements, and MET-14 skipping alterations. These findings highlight that preserving cfRNA in CNB-SS from NSCLC can improve the performance of genomic testing, particularly for RNA-based assays, without compromising the accuracy of DNA-based assays.

P3, N=94, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

Multiple ROS1 tyrosine kinase inhibitors (TKIs)-from crizotinib to newer agents such as entrectinib, lorlatinib, repotrectinib, taletrectinib, and the highly selective zidesamtinib-have improved systemic and intracranial outcomes, although resistance remains inevitable and biologically diverse, involving both on-target kinase mutations and off-target mechanisms...Pemetrexed-based chemotherapy remains an effective option, whereas immune checkpoint inhibitors provide limited benefit...Looking ahead, priorities include optimizing sequencing strategies, evaluating perioperative targeted approaches, and incorporating genomic monitoring to anticipate resistance. These advances are reshaping the natural history of ROS1-rearranged NSCLC and supporting a more durable, precision-driven treatment paradigm.

P2, N=61, Not yet recruiting, Guangdong Association of Clinical Trials