The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid tumors. An investigational drug is one that has not been approved by the U.S. Food & Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.
The goals of this part of the study are:
* Establish a recommended dose of silmitasertib in combination with chemotherapy
* Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer
* To determine the activity of study treatments chosen based on:
* How each subject responds to the study treatment
* How long a subject lives without their disease returning/progressing

Start Date30 Oct 2024

Sponsor / Collaborator

Hershey Medical Center

NCT06202521

/ RecruitingPhase 2

Evaluation of the Safety and Efficacy of Silmitasertib (CX-4945) in Combination With Standard of Care (SOC) for Treating Patients With Community-Acquired Pneumonia (CAP) Associated With SARS-CoV-2 and Influenza Viral Infections

This is a Phase II, multi-center, double-blind, randomized, interventional study in approximately 120 subjects to evaluate clinical benefit of CX-4945 in adult outpatients with SARS-CoV-2 and influenza viral infection-associated pneumonia. The subjects will be recruited into two domains, including SARS-CoV-2 and influenza virus domains. The study will compare the efficacy of Standard of Care (SOC) combined with CX-4945 against SOC paired with a placebo, utilizing a 1:1 allocation ratio in each domain.

Start Date27 Feb 2024

Sponsor / Collaborator

Senhwa Biosciences, Inc.

NCT05817708

/ CompletedPhase 1

A Dose Selection Phase 1 Study Evaluating the Safety and Tolerability of Silmitasertib

This is a Phase I single center, open-label, parallel design in 30 subjects to evaluate safety and tolerability of CX-4945 200mg QD, 200 mg BID and 400mg BID doses (10 subjects in each regimen) for continuously 5 days in healthy subjects for dose selection.

Start Date28 Nov 2022

Sponsor / Collaborator

Senhwa Biosciences, Inc.

100 Clinical Results associated with Silmitasertib

100 Translational Medicine associated with Silmitasertib

100 Patents (Medical) associated with Silmitasertib

361

Literatures (Medical) associated with Silmitasertib

31 Dec 2025·CANCER BIOLOGY & THERAPY

Targeting the IKZF1/BCL-2 axis as a novel therapeutic strategy for treating acute T-cell lymphoblastic leukemia

Article

Author: Li, Jun ; Ye, Chunmei ; Li, Hui ; Li, Juan

OBJECTIVES:

Acute T-cell lymphoblastic leukemia (T-ALL) is a severe hematologic malignancy with limited treatment options and poor long-term survival. This study explores the role of IKZF1 in regulating BCL-2 expression in T-ALL.

METHODS:

CUT&Tag and CUT&Run assays were employed to assess IKZF1 binding to the BCL-2 promoter. IKZF1 overexpression and knockdown experiments were performed in T-ALL cell lines. The effects of CX-4945 and venetoclax, alone and in combination, were evaluated in vitro and in vivo T-ALL models.

RESULTS:

CUT&Tag sequencing identified IKZF1 binding to the BCL-2 promoter, establishing it as a transcriptional repressor. Functional assays demonstrated that IKZF1 overexpression reduced BCL-2 mRNA levels and increased repressive histone marks at the BCL-2 promoter, while IKZF1 knockdown led to elevated BCL-2 expression. CX-4945, a CK2 inhibitor, could reduced BCL-2 levels in T-ALL cells. Notably, knockdown of IKZF1 partially rescued the CX-4945-induced repression of BCL-2. These results underscore the CK2-IKZF1 signaling axis as a key regulator of BCL-2 expression. In vitro, CX-4945 enhanced the cytotoxicity of venetoclax, with the combination showing significant synergistic effects and increased apoptosis in T-ALL cell lines. In vivo studies with cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models demonstrated that CX-4945 and venetoclax combined therapy provided superior therapeutic efficacy, reducing tumor burden and prolonging survival compared to single-agent treatments.

CONCLUSIONS:

IKZF1 represses BCL-2 in T-ALL, and targeting the CK2-IKZF1 axis with CX-4945 and venetoclax offers a promising therapeutic strategy, showing enhanced efficacy and potential as a novel treatment approach for T-ALL.

01 May 2025·ANTIVIRAL RESEARCH

Assessment of repurposed compounds against coronaviruses highlights the antiviral broad-spectrum activity of host-targeting iminosugars and confirms the activity of potent directly acting antivirals

Article

Author: Hill, Michelle L ; Gileadi, Carina ; Brun, Juliane ; Kiappes, J L ; Witt, Karolina D ; Dwek, Raymond A ; von Delft, Annette ; Rangel, Victor ; Arman, Benediktus Yohan ; Makower, Laetitia L ; Zitzmann, Nicole ; Alonzi, Dominic S

The COVID-19 pandemic highlights the need for novel antiviral drug discovery approaches that could dramatically shorten timelines from compound discovery to clinical development. At the beginning of the pandemic, repurposing approaches were at the forefront of early research efforts to screen for antiviral activity against SARS-CoV-2 in over 2500 compounds. Here, we report cellular screening results of 100 FDA-approved and experimental compounds against SARS-CoV-2 in the human Calu-3 cell line. We observed 13 compounds showing antiviral activity against SARS-CoV-2, including seven FDA-approved compounds (remdesivir, boceprevir, amiloride, nafamostat, cisplatin, silmitasertib, and miglustat), and six compounds in pre-clinical and clinical development (tarloxotinib, lucerastat (NB-DGJ), MON-DNJ, NAP-DNJ, NN-DGJ and NN-DNJ). Further, we observed that our screening hits include several host-targeting antivirals, namely iminosugars, that are largely non-toxic and offer a large therapeutic window. The most-developed iminosugar MON-DNJ (UV-4B), which has been evaluated in a Phase 1 clinical trial, shows antiviral activity against SARS-CoV-2 wild type as well as alpha, beta, gamma, delta, and Omicron variants. Its activity also extended to another betacoronavirus HCoV OC43, but not alphacoronavirus HCoV 229E. Our cellular screening results add to the body of knowledge on antivirals against coronaviruses and confirm the antiviral efficacy of iminosugars in cellular assays using the human lung-cell line Calu-3.

27 Mar 2025·BLOOD

Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL

Article

Author: Gu, Yan ; Yang, Yiping ; Lapalombella, Rosa ; Woyach, Jennifer A. ; Dovat, Sinisa ; Li, Jun ; Xiang, Huimin ; Steiner, Chelsea ; Yang, Chan ; Wang, Yan ; Han, Qi ; Zhang, Linyao ; Ge, Zheng ; Song, Chunhua

Abstract:

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a poor prognosis and limited options for targeted therapies. Identifying new molecular targets to develop novel therapeutic strategies is the pressing immediate issue in T-ALL. Here, we observed high expression of WD repeat-containing protein 5 (WDR5) in T-ALL. With in vitro and in vivo models, we demonstrated the oncogenic role of WDR5 in T-ALL by activating cell cycle signaling through its new downstream effector, ATPase family AAA domain-containing 2 (ATAD2). Moreover, the function of a zinc finger transcription factor of the Kruppel family (IKAROS) is often impaired by genetic alteration and casein kinase II (CK2) which is overexpressed in T-ALL. We found that IKAROS directly regulates WDR5 transcription; CK2 inhibitor, CX-4945, strongly suppresses WDR5 expression by restoring IKAROS function. Last, combining CX-4945 with WDR5 inhibitor demonstrates synergistic efficacy in the patient-derived xenograft mouse models. In conclusion, our results demonstrated that WDR5/ATAD2 is a new oncogenic signaling pathway in T-ALL, and simultaneous targeting of WRD5 and CK2/IKAROS has synergistic antileukemic efficacy and represents a promising potential strategy for T-ALL therapy.

News (Medical) associated with Silmitasertib

02 Apr 2025

·www.prnewswire.com

Senhwa Biosciences Announces Positive Clinical Data from Phase 1/Expansion Trial of Silmitasertib (CX-4945) in the Treatment of Basal Cell Carcinoma

Basal Cell Carcinoma CSR Highlights CX-4945 Monotherapy: Progression-free survival (PFS) exceeded 21 months in two patients. Optimal Treatment Response: Three patients achieved partial response (PR), while ten patients had stable disease (SD). Tolerability & Disease Control Rate: Shows potential superiority over current first- and second-line therapies. Unmet Medical Need: Enrolled patients with refractory or recurrent disease who had no remaining treatment options. TAIPEI and SAN DIEGO, April 2, 2025 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that the completion of Clinical Study Report (CSR) for Phase 1/Dose Expansion Trial of Silmitasertib (CX-4945) in the Treatment of Basal Cell Carcinoma(BCC), with positive data outcomes. The study included patients who had relapsed after standard therapies and had no other treatment options. Among them, three patients experienced over 30% tumor reduction (PR), and two patients had a progression-free survival (PFS) exceeding 21 months. CX-4945 significantly prolonged survival in advanced cancer patients, marking a major milestone for both the patients and Senhwa. Compared to current first- and second-line therapies, CX-4945 demonstrated superior tolerability and disease control potential. Therefore, Senhwa will actively pursue licensing possibilities while carefully evaluating CX-4945's potential as a monotherapy or in combination with the second-line immunotherapy Libtayo. The company aims to explore further indications and potential as a first-line treatment, offering better options for patients. Clinical Trial Overview The trial enrolled 25 patients with locally advanced BCC (laBCC, 20 patients) and metastatic BCC (mBCC, 5 patients). The primary objective was to determine the recommended Phase 2 dose (RP2D) and optimal dosing regimen for CX-4945. Among 22 patients eligible for efficacy analysis: Three laBCC patients achieved partial response (PR). Ten patients had stable disease (SD), including 2 mBCC and 8 laBCC patients. Disease control rates: mBCC patients: 80% (4 patients with complete/partial response or stable disease). laBCC patients: 65% (11 patients with complete/partial response or stable disease). Further data analysis showed that: Median progression-free survival (PFS): laBCC: 9.2 months mBCC: 3.7 months Median duration of disease control (DDC): laBCC: 10.3 months mBCC: 7.5 months CX-4945 exhibited promising anti-tumor efficacy and disease stabilization potential in this indication. Additionally, CX-4945 has a lower study drug discontinuation rate of 24% due to AEs, compared to first-line treatments including Vismodegib and Sonidegib, suggesting superior tolerability. Future Prospects This trial is particularly noteworthy as it evaluated CX-4945 monotherapy in patients who had already failed first-line HHIs. Notably, 27.3% (6 patients) had also failed second-line PD-1 inhibitors such as Libtayo or Keytruda. Among the enrolled patients, two advanced-stage patients achieved a progression-free survival (PFS) of over 21 months, lasting 653 days and 667 days, respectively. Notably, the primary lesion of the former patient was almost undetectable by visual inspection. Given the significant potential of CX-4945 as a monotherapy, Senhwa is now actively pursuing regional licensing to accelerate commercialization through strategic partnerships, ultimately benefiting more patients. SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyPhase 1License out/in

07 Nov 2024

·www.outsourcing-pharma.com

Senhwa Biosciences starts trial of silmitasertib in children with difficult to treat cancers

Silmitasertib, also known as CX-4945, was originally developed by Cylene Pharmaceuticals, a San Diego-based biotech that ceased operations in 2013. Since then, Senhwa Biosciences, which is headquartered in Taiwan but also has a San Diego base gained the rights to the small molecule, first in class, casein kinase 2 (CK2) inhibitor. CK2 is overexpressed in a number of tumors. Various studies have shown silmitasertib appears to have good anticancer activity. For example , it triggers autophagy and promote apoptosis of cancer cells in pancreatic and lung cancer and also promotes colorectal cancer cell death. Senhwa is currently testing silmitasertib in early human trials for treatment of cholangiocarcinoma, basal cell carcinoma, medulloblastoma and neuroblastoma. In preclinical studies , the small molecule showed good oral bioavailability and was able to effectively inhibit tumor growth in animal studies while being well tolerated. When combined with DNA-damaging chemotherapy drugs such as gemcitabine and cisplatin, the anticancer activity of silmitasertib seems to be enhanced so it is being tested as an add-on therapy in the new trial. The phase 1/2 study will include 114 children and young adults with relapsed or refractory neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma in the US. "We are thrilled to be able to move this important research forward on a larger scale," said Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium, which is supporting the study. googletag.cmd.push(function () { googletag.display('text-ad1'); }); “The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally.” Additional indication for Covid-19 patients As well as being a promising anti-cancer therapy, silmitasertib is being tested to treat people infected with SARS-CoV-2 who develop serious symptoms that require hospitalization in a phase 2 study. CK2 is involved in regulating signaling pathways important for innate immune responses. Inhibiting this protein kinase can help reduce the excessive cytokine storm immune response often seen in people with severe Covid-19. Studies have shown that silmitasertib and other kinase inhibitors seem to reduce levels of inflammatory biomarkers such as interleukin 6 and tumor necrosis factor-alpha, both of which are high in hospitalized Covid-19 patients. So far results phase 2 results announced by Senhwa have been good with significantly better recovery times observed for Covid-19 patients given silmitasertib versus standard care, with a good safety profile.

Phase 2Clinical ResultPhase 1

06 Nov 2024

·www.prnewswire.com

Senhwa Biosciences announces first patient dosed in the Phase I/II study of Silmitasertib in children and young adults with relapsed refractory solid tumors.

TAIPEI and SAN DIEGO, Nov. 6, 2024 /PRNewswire/ -- Senhwa Biosciences, Inc. (TPEx: 6492), a new drug development company focusing on first-in-class therapeutics for oncology, rare diseases, and infectious diseases, today announced that the enrollment of the first patient at Penn State Health Children's Hospital in its Phase I/II clinical study evaluating the efficacy of Silmitasertib (CX-4945) in combination with chemotherapy for children and young adults with relapsed or refractory solid tumors. This innovative trial seeks to establish a recommended dose of Silmitasertib in combination with chemotherapy and assess the safety, tolerability and efficacy in patients with cancer, with a focus on neuroblastoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma, and liposarcoma. "This clinical trial is a critical piece in understanding the mechanism of how the medicine works and develop more precise treatments for our patients," said Dr. Chandrika Behura, study chair and principal investigator, Four Diamonds researcher and associate professor of pediatrics at the College of Medicine. "It's very important to develop the right combination that can be the most toxic to cancer cells, but the least harmful to the normal cells around them." The study is projected to enroll up to 114 participants nationwide through the Beat Childhood Cancer Research Consortium member hospitals. By evaluating the activity of the study treatments based on individual responses and duration of disease control, the trial aims to develop novel therapeutic approaches. "We are thrilled to be able to move this important research forward on a larger scale," said Dr. Giselle Sholler, division chief of pediatric hematology/oncology and director of pediatric oncology research at the College of Medicine and chairperson of the Beat Childhood Cancer Research Consortium. "The insights gained from this trial will help not only local patients and their families but can lead to new therapies that can help children throughout the US and internationally." With the College of Medicine serving as its home, the Beat Childhood Cancer Research Consortium is a worldwide network of more than 50 universities and children's hospitals focused on saving lives and helping the Children's Hospital make a lasting difference around the world. Funding for this clinical trial is provided by the Beat Childhood Cancer Foundation and the Little Warrior Foundation. Funding for Behura's research which led to the clinical trial was provided by Four Diamonds. "This is the culmination of the work of many people over the years," said Suzanne Graney, executive director of Four Diamonds. "Without the dedication of our physician-scientists and the generosity of our donors and community, this kind of essential work to improve treatments with an ultimate goal of curing cancer would not be possible." The pediatric cancer care specialists at Beat Childhood Cancer Research Consortium hospitals and researchers at the College of Medicine are dedicated to turning groundbreaking discoveries into lifesaving treatments for childhood cancer. "By expanding our research and increasing clinical trials, we are exploring immunotherapy, cellular therapy and precision medicine to deliver the most optimized care to each unique patient," said Dr. Dr. Yatin Vyas, pediatrician-in-chief and chair of the Department of Pediatrics at the Children's Hospital. "We are greatly honored to collaborate with the Penn State College of Medicine and Beat Childhood Cancer Research Consortium, which have been diligently fighting childhood cancers by infusing invaluable resources from over 50 universities and children's hospitals across the United States for the clinical study," said Jin-Ding Huang, PhD, CEO of Senhwa Biosciences, Inc. "We appreciate for having the opportunity of providing Silmitasertib as a potential effective treatment and look forward to realizing its therapeutic value in this urgently needed field for childhood cancers though this study". SOURCE Senhwa Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical StudyImmunotherapy

100 Deals associated with Silmitasertib

External Link

KEGG	Wiki	ATC	Drug Bank
-	Silmitasertib	-	DB15408

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Ewing Sarcoma	Phase 2	United States	Senhwa Biosciences, Inc.	06 Nov 2024
Liposarcoma	Phase 2	United States	Senhwa Biosciences, Inc.	06 Nov 2024
Rhabdomyosarcoma	Phase 2	United States	Senhwa Biosciences, Inc.	06 Nov 2024
Influenza A virus infection	Phase 2	Taiwan Province	Senhwa Biosciences, Inc.	27 Feb 2024
Community Acquired Pneumonia	Phase 2	Taiwan Province	Senhwa Biosciences, Inc.	27 Feb 2024
COVID-19	Phase 2	United States	Senhwa Biosciences, Inc.	30 Nov 2020
Recurrent Medulloblastoma	Phase 2	United States	Senhwa Biosciences, Inc.	25 Jul 2019
Bile Duct Neoplasms	Phase 2	United States	Senhwa Biosciences, Inc.	-
Bile Duct Neoplasms	Phase 2	South Korea	Senhwa Biosciences, Inc.	-
Bile Duct Neoplasms	Phase 2	Taiwan Province	Senhwa Biosciences, Inc.	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05817708 (CTgov)	Phase 1	COVID-19	30	CX-4945 (CX-4945 200mg QD)	vxextwkqgk = fjawpqmqfr cfjqrxfxpy (jslkmwcnyw, dcebddjmzm - pcluwrqmug) View more	-	27 Jan 2025
				CX-4945 (CX-4945 200mg BID)	vxextwkqgk = tixmkkhcki cfjqrxfxpy (jslkmwcnyw, kyqicinhhh - xvxwhnjbqm) View more
NCT04663737 (CTgov)	Phase 2	COVID-19	20	Silmitasertib (Group A)	qmhodbkqbk = bfpofdwcaj ccqgtmsicq (spbwtkpsyt, atrsjfmqig - wwndvwzchc) View more	-	16 Dec 2024
				SOC (Group B)	qmhodbkqbk = alsdzhxhaw ccqgtmsicq (spbwtkpsyt, yghuwmvkxx - gbdfpeokjx) View more
NCT02128282 (S4-13-001, Pubmed) Manual	Phase 1/2	Bile Duct Neoplasms First line	84	Gemcitabine+Cisplatin+Silmitasertib	wzhabfznbq(yxqegtgnob) = kyhbglvxvu ejbgiudoya (anrswfrtme, 7.6 - 14.7) View more	Positive	24 Sep 2022
				Gemcitabine+Cisplatin	wzhabfznbq(yxqegtgnob) = lovikeutel ejbgiudoya (anrswfrtme, 3.1 - NE) View more
NCT04663737 (Biospace) Manual	Phase 2	COVID-19	20	CX-4945	yyacpphxiw(swxyyokuya) = tpgoanrrvh oytngvenqc (xskvoobbro ) View more	Positive	20 Oct 2021
				Standard of Care	cgprhwnlzo(mqieatulpz) = pibkrvxlhv hhuijhobcl (txvjhflukd ) View more
NCT02128282 (S4-13-001, ASCO_GI 12021 \| ASCO_GI 22021) Manual	Phase 1/2	Metastatic Cholangiocarcinoma First line	87	gemcitabine+cisplatin+Silmitasertib	mdbbealfpt(vyjxuxmrrx) = dbxhvuarfj zxqrmuamzr (gzshnfchnv, 7.6 - 14.7) View more	Positive	22 Jan 2021
OR02-2 (ENDO2019)	Not Applicable	Adrenocortical Carcinoma NR5A1	-	CX-4945	zqirvndqqr(ckytwmzsjl) = jsfcygrojz flksyrwzgm (atqzkhbbsv )	Positive	30 Apr 2019
NCT02128282 (ASCO_GI2017)	Phase 1/2	Advanced biliary tract cancer	127	CX-4945	fakbpmmciy(rcibuvhwxd) = snepkmsesg cltncobito (ctdwfswpjp ) View more	-	21 Mar 2017

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