ROS1 wild-type

P1, N=56, Completed, Haihe Biopharma Co., Ltd. | Unknown status --> Completed | N=113 --> 56

P2, N=1, Terminated, Ralph G Zinner | N=37 --> 1 | Trial completion date: Aug 2027 --> Jul 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Jul 2024; Slow accrual

P2, N=42, Recruiting, Georgetown University | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: Jul 2024 --> Dec 2024

While crizotinib and entrectinib have been approved to treat ROS1 fusion-positive (ROS1+) non-small-cell lung cancer (NSCLC), unmet needs remain. Taltrectinib has the potential to improve PFS based on its greater potency against ROS1+ tumors and high CNS penetration. By selectively inhibiting ROS1 wild-type and its resistant mutations over TRKB, taltrectinib has a better safety profile with minimal CNS-related AEs compared to other ROS1+ inhibitors.

Combination treatment with the chemotherapeutic agent temozolomide and an inhibitor of ROS1, JAK2, or a downstream target of STAT3, demonstrated antitumor effects against KLC1-ROS1 fusion-expressing glioma cells. Our results demonstrate that KLC1-ROS1 fusion exerts oncogenic activity through serum-independent constitutive activation, resulting in specific activation of the JAK-STAT pathway. Our data suggested that molecules other than RTKs may serve as novel therapeutic targets for RTK fusion in gliomas.

P2, N=37, Recruiting, Ralph G Zinner | Not yet recruiting --> Recruiting

P2, N=37, Not yet recruiting, Ralph G Zinner

Conclusions We identified that ROS1 mutation predicted the resistance to ICIs in HNSCs. The clinical delivery of ICIs should be cautious in those patients.

With the limitations of the retrospective analysis, the proposed LIPI-based score seems to predict OS with P and PCT. Prospective validation is required.

This article summarizes the most up-to-date trial data on treatments for driver-negative advanced non-small cell lung cancer, including immunotherapy monotherapy, chemoimmunotherapy, and combination immunotherapy, providing a framework for clinicians based on PD-L1 and smoking status. A multibiomarker assay that may best predict immunotherapy response remains an active area of research.

P2, N=42, Recruiting, Georgetown University | Trial primary completion date: Jul 2023 --> Jul 2024

Our study confirms low frequency and histotype diversity of NTRK fusion in STS. While the activity of TRKi in simple genomics NMT is confirmed, our clinical data encourage subsequent studies focusing on the biological relevance of NTRK fusions in sarcomas with complex genomics together with the efficacy of TRKi in this population.

P1, N=40, Recruiting, Peter MacCallum Cancer Centre, Australia | Initiation date: Oct 2022 --> Jan 2022

We have mapped the activated oncogenic pathways of a novel ROS1-fusion gene and broadened the knowledge of the newly recognized infant-type glioma subtype. The finding facilitates suitable targeted therapies for the patient in case of relapse.

Molecularly targeted treatment with crizotinib induced a rapid and sustained partial response...In summary, the high prevalence of GOPC-ROS1 and noncanonical ROS1 fusions pose diagnostic challenges. We advocate NGS-based comprehensive molecular profiling of MSS CRCs that are wild type for RAS and BRAF and patient enrollment in precision trials.

P1, N=40, Recruiting, Peter MacCallum Cancer Centre, Australia | Not yet recruiting --> Recruiting | Initiation date: Apr 2022 --> Oct 2022

P2, N=29, Recruiting, Hunan Cancer Hospital

P2; N=42; Recruiting; Sponsor: Georgetown University; Not yet recruiting ➔ Recruiting