P2, N=49, Not yet recruiting, University of Miami | Trial completion date: Nov 2029 --> Feb 2030 | Trial primary completion date: Nov 2029 --> Feb 2030

P1, N=10, Completed, Blueprint Medicines Corporation | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> May 2024

More importantly, we found that Proguanil's inhibitory effect on U87MG cell growth and migration was positively correlated with CSF1R expression, and this effect diminished following CSF1R knockdown and Proguanil demonstrated synergistic effects with CSF1R-targeting positive drugs (BLZ945 and GW2580). Meanwhile, Proguanil targeted CSF1R to inhibit M2-type polarization of tumor-associated macrophages (TAMs) and their proliferation, thus altering the tumor microenvironment while indirectly suppressing the proliferation and migration of U87MG cells. Taken together, these findings suggest that Proguanil may serve as a promising CSF1R antagonist for GBM treatment.

P3, N=184, Completed, Chipscreen Biosciences, Ltd. | Recruiting --> Completed | Trial completion date: Dec 2025 --> Apr 2024 | Trial primary completion date: Dec 2024 --> Apr 2024

P3, N=240, Recruiting, Incyte Corporation | Not yet recruiting --> Recruiting

Although there remains interest in agents targeting CSF-1, hepatic toxicity appears to be a limiting factor for their use in early breast cancer.

P1/2, N=44, Not yet recruiting, The University of Texas Health Science Center at San Antonio | Initiation date: Sep 2024 --> Jan 2025

P1, N=72, Not yet recruiting, Incyte Corporation

P1, N=15, Not yet recruiting, Washington University School of Medicine | Trial completion date: Oct 2028 --> Jan 2029 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Nov 2026 --> Feb 2027

P3, N=180, Recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Dec 2024 --> Dec 2025

Additionally, pacritinib preventive treatment reduced COL1A1 production in an in vitro model mimicking JAK2-driven fibrosis. These findings highlight that dual inhibition of JAK2/IRAK1 with pacritinib, by delaying or attenuating the myelofibrotic progression, could be a potential modifier of the natural course of MPN.

P1, N=78, Active, not recruiting, Qurient Co., Ltd. | Recruiting --> Active, not recruiting

P1/2, N=41, Active, not recruiting, Syndax Pharmaceuticals | Trial completion date: Dec 2023 --> Dec 2024

P4, N=2, Completed, Blueprint Medicines Corporation | Active, not recruiting --> Completed

P1/2, N=72, Not yet recruiting, Hangzhou Hanx Biopharmaceuticals, Ltd.

We report three patients with histiocytic disorders harboring novel alterations who had sustained responses to off-label kinase inhibitors specific to their histiocytic disorder. Pathogenic variants outside of the MAPK pathway, including variants of unknown significant, may be targeted with readily available small molecules.

P2, N=9, Terminated, Chipscreen Biosciences, Ltd. | N=38 --> 9 | Recruiting --> Terminated; During the enrollment period of this project, due to the increasing proportion of patients receiving capecitabine adjuvant therapy and the large number of trials competing for the same number of lines in various centers

P=N/A, N=6, Completed, Daiichi Sankyo Co., Ltd. | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Oct 2024

P1, N=26, Not yet recruiting, Abbisko Therapeutics Co, Ltd

Furthermore, depletion of microglia by PLX3397, a colony-stimulating factor 1 receptor inhibitor, ameliorated cognitive dysfunction. These results suggest that microglia mediate periodontal infection-induced cognitive dysfunction in obesity.

P=N/A, N=61, Completed, CStone Pharmaceuticals | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Sep 2024 | Trial primary completion date: May 2025 --> Sep 2024

P1/2, N=380, Not yet recruiting, Shanghai Runshi Pharmaceutical Technology Co., Ltd

P1, N=60, Not yet recruiting, The First Affiliated Hospital of Henan University of Science and Technology; The First Affiliated Hospital of Henan University of Science and Technolo

P2, N=6, Terminated, Medical College of Wisconsin | Trial completion date: May 2027 --> Oct 2024 | Active, not recruiting --> Terminated; After 6 patients were enrolled, it was determined that only patients with STAT5 activation were having a biochemical response to pacritinib treatment.

P1, N=19, Completed, Shanghai Runshi Pharmaceutical Technology Co., Ltd | Not yet recruiting --> Completed

P=N/A, N=39, Recruiting, Jinling Hospital, China

P2, N=36, Recruiting, Deciphera Pharmaceuticals, LLC | Not yet recruiting --> Recruiting

P1, N=10, Not yet recruiting, City of Hope Medical Center

Collectively, our study showed PLX-3397-related efficacy in ameliorating pain linked to the reduction of microglia and neuroinflammation in mice. Furthermore, our research provided new proof-of-concept data supporting the promise of testing PLX-3397 as an analgesic.

P1/2, N=52, Recruiting, Uma Borate | Not yet recruiting --> Recruiting

P2, N=49, Not yet recruiting, University of Miami

P2, N=9, Suspended, University of Utah | Recruiting --> Suspended

P3, N=450, Not yet recruiting, Shanghai Runshi Pharmaceutical Technology Co., Ltd

These results underscore an additional pharmacological benefit of edicotinib against ABCG2 activity, suggesting its potential incorporation into combination therapies for patients with ABCG2-overexpressing tumors. Further research is warranted to validate these findings and explore their clinical implications.

P1, N=24, Enrolling by invitation, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Enrolling by invitation

In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781.

This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST.

P2, N=241, Active, not recruiting, Syndax Pharmaceuticals | Trial completion date: Dec 2024 --> Sep 2027

Interestingly, pacritinib, but not other JAK inhibitors such as ruxolitinib, upadacitinib, or filgotinib, acted synergistically with lenvatinib in HCC cells. Immunohistochemical analysis of tumor sections revealed that pacritinib reduced Ki67 staining and phosphorylated IRAK1. Our findings suggest that pacritinib may be a promising therapeutic option for the treatment of advanced HCC, particularly in patients who have developed resistance to lenvatinib.

P1/2, N=88, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Apr 2024

P2, N=36, Not yet recruiting, Deciphera Pharmaceuticals, LLC

P2, N=15, Not yet recruiting, M.D. Anderson Cancer Center