Jakafi (ruxolitinib)

P1, N=30, Recruiting, Oncotherapeutics | Not yet recruiting --> Recruiting | Initiation date: Jan 2024 --> Dec 2022

These include new JAK inhibitors with greater specificity for JAK2, as well as "add-on" medications designed to enhance the effectiveness of ruxolitinib, in both patients who are new to the drug and in those who have shown suboptimal responses. Additionally, there is ongoing exploration of novel therapeutic targets. In this review, we will explore the immunotherapy approaches that are currently used in clinical practice for MPNs, as well as emerging strategies that are likely to change the treatment of these diseases in the coming years.

Upon ruxolitinib withdrawal, TSLPRCART functionality recovered in vivo with clearance of subsequent ALL rechallenge. These translational studies demonstrate an effective two-pronged therapeutic strategy that mitigates acute CART-induced hyperinflammation and provides potential anti-leukemia 'maintenance' relapse prevention for CRLF2-rearranged Ph-like and DS-ALL.

Finally, disease hallmarks in MPL W515L -transplanted mice were attenuated upon treatment with the autophagy inhibitor hydroxychloroquine or the ROCK inhibitor Y27632, either as monotherapy or in combination with the JAK2 inhibitor ruxolitinib. Overall, our data indicate that aberrant cytokine secretion is dependent on secretory autophagy downstream of RhoA, targeting of which represents a novel therapeutic avenue in the treatment of myelofibrosis. TGFβ1 is released from megakaryocytes via RhoA-mediated secretory autophagy, and targeting this process can alleviate fibrosis progression in a preclinical mouse model of myelofibrosis.

P1/2, N=1, Active, not recruiting, National Heart, Lung, and Blood Institute (NHLBI) | Recruiting --> Active, not recruiting

P3, N=38, Terminated, Celgene | Completed --> Terminated; Slow accrual.

Anemia and interstitial pneumonia both significantly improved following treatment with a Janus kinase 2 gene inhibitor. In this report, we discuss the possible mechanisms underlying PMF complicated with ILD.

Mechanistically, H19 competitively binds to the mRNA of YTHDC1 with MiR-107, and also interacts with the YTHDC1 protein, regulating the stability of SRSF1 and thereby affecting the alternative splicing of IL-6 and IL-10. Utilizing organoids and the patient-derived xenograft (PDX) model, it is found that ruxolitinib may represent a promising treatment option for PDAC patients with high H19 expression.

An osimertinib and ICI-induced irAE mouse model was constructed that showed osimertinib combined with ICIs inhibited EGFR phosphorylation and activated the IL-6/JAK/STAT3 signaling pathway in mouse liver macrophages, which led to the release of relevant cytokines.

These include single-agent brentuximab vedotin, histone deacetylase inhibitors, duvelisib, ruxolitinib, EZH2 inhibitors, and azacitidine, among others. Follicular helper T-cell lymphomas, given frequent mutations in epigenetic regulator genes, may preferentially respond to agents such as histone deacetylase inhibitors, EZH2 inhibitors, and hypomethylating agents. As these therapies evolve in their use for both relapsed/refractory disease and then into frontline treatment, subtype-specific therapy will likely help personalize care for patients with PTCL.

P2, N=115, Completed, Institute of Hematology & Blood Diseases Hospital, China | Recruiting --> Completed | Trial completion date: Dec 2025 --> Dec 2024

P3, N=210, Recruiting, medac GmbH | Trial completion date: Dec 2027 --> Aug 2030 | Trial primary completion date: Dec 2025 --> Aug 2027

P1/2, N=2, Terminated, St. Petersburg State Pavlov Medical University | N=20 --> 2 | Trial completion date: Dec 2025 --> Nov 2024 | Recruiting --> Terminated; Poor recruitment

P1, N=231, Recruiting, Incyte Corporation | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Nov 2024 --> Dec 2025

In fact, the use of selective JAK1 inhibitors ruxolitinib or baricitinib inhibited the induction of ISG's and the proliferation of p53 and ARF deleted cells. We identify a group of solid human tumors that lack functional p53 and ARF, show an expression signature of the upregulated type I IFN response genes, and are sensitive to selective JAK1 inhibitors. These data suggest that the type I IFN response acts as a positive driver of proliferation in the absence of p53 and ARF and, as such, presents itself as a potential therapeutic target in aggressive solid tumors.

Co-treatment with SY-5609 and ruxolitinib was synergistically lethal in HEL, SET2 and PD post-MPN-sAML cells.  A CRISPR screen in SET2 and HEL cells revealed BRD4, CBP and p300 as co-dependencies with SY-5609 treatment. Accordingly, co-treatment with SY-5609 and the BETi OTX015 or pelabresib or with the CBP/p300 inhibitor GNE-049 was synergistically lethal in MPN-sAML cells (including those exhibiting TP53 loss). Finally, in the HEL-Luc/GFP xenograft model, compared to each agent alone, co-treatment with SY-5609 and OTX015 reduced post-MPN-sAML burden and improved survival without inducing host toxicity. These findings demonstrate promising preclinical activity of the CDK7i-based combinations with BETi or HATi against advanced-MPNs, including post-MPN-sAML.

P1, N=30, Recruiting, Children's Hospital Medical Center, Cincinnati

Ruxolitinib is a Janus kinase inhibitor that can alleviate pruritus and decrease splenomegaly in patients who are intolerant of or resistant to hydroxyurea. To decrease the risk of thrombosis, all patients with PV should be treated with aspirin and therapeutic phlebotomy to maintain a hematocrit of less than 45%. Cytoreductive therapies, such as hydroxyurea or interferon, are recommended for patients at high risk of thrombosis.

P3, N=586, Recruiting, University of Birmingham | Trial completion date: Feb 2028 --> Apr 2030 | Trial primary completion date: Aug 2026 --> Oct 2028

Next, we used clinically available signal inhibitors (MEK inhibitor trametinib, JAK inhibitor ruxolitinib, and JNK inhibitor SP600125), and found that ruxolitinib inhibits AMIGO2 expression more stably. Using the MKN45 gastric cancer cells, we confirmed that ruxolitinib could prevent liver metastasis of human cancer cells. These results demonstrate that pharmacological inhibition of AMIGO2 expression in tumor cells is a promising novel strategy to prevent and control liver metastasis.

These novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators.

P=N/A, N=28, Not yet recruiting, The First Affiliated Hospital, School of Medicine, Zhejiang University; The First Affiliated Hospital, College of Medicine, Zhejiang University

P2, N=82, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P2, N=40, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Trial primary completion date: Jun 2024 --> Oct 2024

P2, N=102, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Trial primary completion date: Jun 2024 --> Oct 2024

P2, N=41, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jan 2025 --> Dec 2026 | Trial primary completion date: Jan 2025 --> Dec 2025

P2, N=112, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=200 --> 112

P2, N=16, Terminated, University of California, San Francisco | Completed --> Terminated; Low accrual

P2, N=28, Recruiting, Jonathan Brammer | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=120, Not yet recruiting, H. Lee Moffitt Cancer Center and Research Institute

Our results revealed the relationships among the ERα, PI3K/AKT, and MAPK signaling pathways in ER+ breast cancer cells. Understanding the interactions among ERα, PI3K-AKT-mTOR, and MAPK could lead to novel combination therapies.

P1/2, N=147, Active, not recruiting, NRG Oncology | Trial completion date: Sep 2022 --> Aug 2025

P2, N=200, Recruiting, Incyte Corporation | Trial completion date: Sep 2024 --> Sep 2027 | Trial primary completion date: Sep 2024 --> Sep 2027

Current therapeutic strategies include JAK inhibitors like Ruxolitinib, which target the JAK-STAT pathway, alongside supportive treatments such as blood transfusions, erythropoiesis-stimulating agents and developing combinatorial approaches...Recently approved JAK inhibitors, including Fedratinib, Pacritinib, and Momelotinib, have expanded the therapeutic landscape...These technologies elucidate the role of the spleen in MF, highlighting its transformation into a site of abnormal hematopoietic activity, fibrotic changes, and immune cell infiltration, functioning as a "tumor surrogate." By profiling diverse cell populations and molecular alterations within the BM and spleen, SRT facilitates a deeper understanding of MF pathophysiology, helping identify novel therapeutic targets and biomarkers. Ultimately, integrating spatial transcriptomics into MF research promises to enhance diagnostic precision and therapeutic innovation, addressing the multifaceted challenges of this disease.

Various therapies have been discovered for psoriasis, including topical treatments, phototherapy, conventional systemic agents such as methotrexate, retinoids and ciclosporine, as well as biologics...Ruxolitinib cream has been investigated in various dermatologic diseases, including atopic dermatitis, vitiligo, psoriasis, and alopecia areata. However, there is limited data on the efficacy of oral ruxolitinib in patients with psoriasis vulgaris. Here, we report a patient diagnosed with myelofibrosis coexisting with psoriasis vulgaris, successfully treated with oral ruxolitinib.

P1/2, N=54, Recruiting, Veronika Bachanova | Trial completion date: Dec 2026 --> Jul 2027 | Trial primary completion date: Sep 2024 --> Jul 2025

P1/2, N=55, Recruiting, Masonic Cancer Center, University of Minnesota | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=23, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Aug 2024 --> Dec 2024

Notably, pleural effusion and mediastinal mass significantly improved the post-chest cavity infusion of dexamethasone combined with etoposide at the same stage. The patient also underwent allogeneic hematopoietic stem cell transplantation upon achieving bone marrow remission and was followed up until January 2024. Ruxolitinib combined with venetoclax and azacytidine has shown promising efficacy and safety in treating refractory T-ALL harboring the JAK1, JAK3, and STAT5B mutations, providing a novel therapeutic approach for such patients.

P3, N=66, Active, not recruiting, MaaT Pharma | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Nov 2025 | Trial primary completion date: Sep 2023 --> Nov 2024

P1, N=18, Recruiting, University of Chicago | Not yet recruiting --> Recruiting

P2, N=36, Recruiting, Aaron Logan, MD | Not yet recruiting --> Recruiting | Trial completion date: May 2027 --> Nov 2027 | Initiation date: Feb 2024 --> Oct 2024 | Trial primary completion date: May 2027 --> Nov 2027