This study is being done to answer the following question: Can testing breast cancer for DNA abnormalities or "biomarkers" help predict which patients are most likely to be helped by certain treatments? The pre-study screening is being done to test a sample of blood (or tumour tissue) for biomarkers to see if patients can participate in the study

Start Date13 Jun 2023

Sponsor / Collaborator

Canadian Cancer Trials Group

NCT05251714

/ Active, not recruitingPhase 1/2

A Dose-confirming Study of CFI-402257 as a Single Agent in Advanced Solid Tumors and in Combination With Fulvestrant in Patients With ER+/HER2- Advanced Breast Cancer After Disease Progression on Prior CDK4/6 and Endocrine Therapy

The purpose of this study is to test the safety of an investigational drug called CFI-402257 alone in advanced solid tumors and in combination with Fulvestrant in advanced breast cancer patients.

Start Date27 May 2022

Sponsor / Collaborator

Treadwell Therapeutics, Inc.

NCT03568422

/ Active, not recruitingPhase 1/2IIT

A Phase Ib and Open Label Phase II Study of CFI-402257 in Combination With Weekly Paclitaxel in Patients With Advanced/Metastatic HER2-Negative Breast Cancer

The standard or usual treatment for this disease is to undergo chemotherapy to slow the spread of disease and relieve some symptoms of cancer. One of the standard types of chemotherapy is a drug called paclitaxel (Taxol) given in a low dose every week for three out of four weeks.
CFI-402257 is a new type of drug for breast cancer. Laboratory tests show that it may help slow the growth of breast cancer. This drug has been shown to shrink tumours in animals. CFI-402257 has been studied in a few people and appears well tolerated with little side effects. CFI-402257 seems promising but it is not clear if it can offer better results when given with paclitaxel compared to paclitaxel alone.

Start Date05 Feb 2019

Sponsor / Collaborator

Canadian Cancer Trials Group

[+3]

100 Clinical Results associated with CFI-402257

100 Translational Medicine associated with CFI-402257

100 Patents (Medical) associated with CFI-402257

Literatures (Medical) associated with CFI-402257

01 Oct 2026·COMPUTATIONAL BIOLOGY AND CHEMISTRY

Computational exploration of quercetin derivatives from Azadirachta indica leaf as threonine tyrosine kinase inhibitors for potential lung and pancreatic cancer treatment

Article

Author: Sarker, Susen ; Al Imran, A Q M ; Hossain, Md Rezoan ; Priya, Samsun Nahar ; Al Ashik, Sheikh Abdullah

Lung and pancreatic adenocarcinomas account for substantial cancer-related mortality worldwide, with current therapeutic efficacy severely limited by the development of high drug resistance. Threonine tyrosine kinase (TTK) has emerged as both a therapeutic target and a critical prognostic marker in these malignancies, with elevated expression correlating strongly with poor clinical outcomes. Therefore, this study aimed to investigate natural quercetin derivatives from Azadirachta indica leaf as novel TTK inhibitors through comprehensive computational approaches. From initial TTK expression and survival analyses to subsequent Molecular docking, machine learning models predicted bioactivity estimation, quantum chemical calculations, molecular dynamics (MD) simulations, post-dynamics MM-PBSA calculations, and in silico toxicity profiling were performed to identify TTK inhibitors. TTK overexpression significantly correlated with diminished survival in both cancer types (hazard ratios: 1.5-2.0). Quercetin-3-rhamnoside, quercetin-3-glucoside, quercetin-3-O-galactoside, and quercetin-3-rutinoside demonstrated superior binding affinities (-9.5 to -11.089 kcal/mol) compared to control drug Luvixasertib (-8.869 kcal/mol), with enhanced electronic properties (electrophilicity index: 3.53-4.67 compared to control 2.70). Furthermore, Machine learning predictions demonstrated promising bioactivity (pIC₅₀: 6.915-7.835), while 200 ns MD simulations confirmed structural stability with optimal RMSD (1.419-2.035 Å). Subsequently, MM-PBSA calculations revealed markedly favorable binding free energies for quercetin-3-rhamnoside and quercetin-3-glucoside (-33.104 and -32.676 kcal/mol) compared to control (-28.430 kcal/mol). Additionally, toxicity profiling revealed favorable safety profiles with no hepatotoxic, carcinogenic, or mutagenic potential for most derivatives. Therefore, Quercetin derivatives from A. indica leaf represent promising lead compounds for targeted TTK inhibitors in lung and pancreatic adenocarcinomas, highlighting their potential for further experimental validation against TTK.

01 Aug 2026·INTERNATIONAL IMMUNOPHARMACOLOGY

cGAS-STING Signalling in the tumour microenvironment: Implications for immune surveillance and therapeutic strategies

Review

Author: Rahiman, Siti Sarah Fazalul ; Murugaiyah, Vikneswaran ; Al-Ramamneh, Rahmeh Saad ; Attiq, Ali ; Mohamed, Rafeezul ; Ahmad, Waqas ; Afzal, Sheryar ; Al-Adayleh, Teeb Yasir Mahmoud

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway links cytosolic DNA sensing to type I interferon production and inflammatory signalling, making it central to innate immunity. In addition to defending against pathogens, it shapes the tumour microenvironment by regulating immune surveillance, antitumour activity, and tumour progression. Short-term cGAS-STING activation enhances dendritic cell maturation, antigen presentation, macrophage polarisation, and cytotoxic lymphocyte recruitment. However, prolonged activation shifts the TME into an immunosuppressive state by inducing NF-κB-mediated inflammation, expanding regulatory T cells, increasing myeloid-derived suppressor cell accumulation, and elevating immune checkpoint expression. Crosstalk among the STAT3, TGF-β, and autophagy pathways further impacts angiogenesis, fibrosis, and metastasis. Additionally, metabolic stress, mitochondrial DNA (mtDNA) release, and epigenetic silencing of pathway components under hypoxic or chromosomally unstable conditions modify STING responsiveness, ultimately affecting therapeutic outcomes. Pharmacological activation using cyclic dinucleotides (CDN) STING agonists (ADU-S100 and MK-1454) and non-CDN STING agonists (diABZI and MSA-2), as well as MPS1 inhibitors (CFI-402257, BAY-1217389, and CC-671), has effectively triggered strong type I interferon responses and caused tumour regression in preclinical and clinical trials. When combined with radiotherapy, PARP inhibitors, or immune checkpoint blockers, these agents exhibit enhanced synergy but are constrained by tumour heterogeneity and context-dependent toxicity. Here, we reviewed the complexity of the cGAS-STING and its potential as a double-edged sword in cancer treatment, underscoring the need for strict strategies to harness this pathway while enhancing antitumour immunity and mitigating pro-tumorigenic effects.

01 Aug 2025·NEOPLASIA

Targeting monopolar spindle kinase I (Mps1 or TTK) induces radiosensitization in syngeneic models of triple negative breast cancer (TNBC) and potentiates type I interferon (T1IFN) signaling

Article

Author: Wilson, Cydnee M ; Rae, James M ; Jungles, Kassidy M ; Liu, Meilan ; Speers, Corey W ; Wilder-Romans, Kari ; Jungles, Kalli R ; Pierce, Lori J ; Bishop, Caroline R

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately impacts Black women and has limited effective therapeutic options. Consequently, there is an urgent need to develop novel approaches for the treatment of TNBC. Previously, we identified monopolar spindle kinase I (Mps1 or TTK), which is upregulated in TNBC patients after radiotherapy, as a potential therapeutic target. We found that TTK inhibition sensitizes human TNBC to radiotherapy (RT) both in vitro and in vivo; however, these studies were performed in immunodeficient models. Here, we extended those studies into syngeneic murine models of TNBC using two TTK inhibitors: empesertib and the novel TTK inhibitor CFI-402257 (also known as luvixasertib) that was recently granted FDA fast track approval in breast cancer. These studies demonstrate that TTK inhibition radiosensitizes syngeneic murine models of TNBC and increases the production of micronuclei and aneuploidy. Mechanistic studies demonstrate that TTK inhibition and RT alter the tumor immune microenvironment of TNBC by modifying the production of antitumoral type I interferon (T1IFN). In vivo, TTK inhibition sensitizes syngeneic models of TNBC to RT. Furthermore, combining TTK inhibition and RT also potentiates T1IFN signaling, suggesting that combination treatment may induce antitumoral immunity in immunocompetent models. Taken together, these studies demonstrate that TTK inhibition enhances radiosensitivity and TTK inhibition with RT modulates the immune landscape of TNBC. Collectively, this combination may represent a novel therapeutic strategy to improve outcomes for patients with TNBC by both direct tumor cytotoxicity and by promoting an immune-responsive environment.

News (Medical) associated with CFI-402257

20 Feb 2024

·www.biospace.com

Treadwell Announces Ocifisertib, a First-in-Class PLK4 Inhibitor, has Received Orphan Designation from U.S. FDA for the Treatment of Acute Myeloid Leukemia

With a Focus on Potential Pivotal Studies in 2025, Treadwell has Strengthened its Leadership Team by Appointing Brenda Marczi, PharmD, MBA as SVP and Head of Regulatory Affairs TORONTO & SAN FRANCISCO--(BUSINESS WIRE)-- Treadwell Therapeutics, a privately held clinical-stage biotechnology company pioneering and advancing novel first-in-class medicines for unmet needs in cancer, today announced the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to ocifisertib (CFI-400945), a first-in-class, investigational PLK4 inhibitor for the treatment of acute myeloid leukemia (AML). Ocifisertib is currently being evaluated in a Phase 1b/2 study in adults with relapsed/refractory AML following standard of care therapy. Orphan drug designation is granted by the FDA to drugs intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the U.S. at the time of designation. Under the FDA’s Orphan Drug Act, orphan drug status provides incentives, grants, tax credits and waiver of certain administrative fees as well as seven years of market exclusivity following marketing authorization. Treadwell also announced today the appointment of Brenda Marczi, as SVP and Head of Regulatory Affairs. Brenda comes to Treadwell with over 30 years of regulatory experience in the pharmaceutical and biotechnology industries. She most recently served as Senior Vice President, Regulatory Affairs at Tracon Pharmaceuticals, Inc., where she oversaw their regulatory function and led all of their strategies and filing activities in the US and UK. Brenda holds a Master of Science in Pharmaceutical Sciences from Rutgers University, a PharmD from the University of Maryland, and an MBA from Wharton, University of Pennsylvania. “The FDA’s decision to grant orphan drug designation, along with the previous FDA Fast Track designation for ocifisertib underscores Treadwell’s dedication to addressing this patient population with few treatment options. Patients with relapsed and/or refractory AML, in particular TP53 mutated disease suffer poor overall survival and represents a high unmet clinical need,” said Roger Sidhu, M.D., Acting CEO of Treadwell. “We look forward to advancing ocifisertib in partnership with investigators, regulators, patients and their families for those with limited treatment options in tough to treat AML. In addition, we are thrilled to have Brenda join us to lead Regulatory Affairs at Treadwell. She is a seasoned strategic leader with a broad experience in leading regulatory strategy from early development through approval. Her leadership will be invaluable to Treadwell as we advance ocifisertib into potentially pivotal studies in 2025.” About Treadwell Therapeutics Treadwell Therapeutics is a clinical-stage oncology company developing novel medicines to address unmet needs in patients with cancer. The Company's robust, internally developed clinical pipeline includes ocifisertib (PLK4 inhibitor), CFI-402257 (TTK/Mps1 inhibitor) and CFI-402411 (HPK1 inhibitor). Treadwell also has a broad pre-clinical pipeline with multiple biologic and next generation TCR based autologous cell therapy programs. For more information, please visit .

Orphan DrugFast Track

15 Dec 2023

·www.biospace.com

Treadwell Therapeutics Announces a Presentation at the 2023 ASH Annual Meeting and Advisory Board Meeting

TORONTO and SAN MATEO, Calif., Dec. 15, 2023 (GLOBE NEWSWIRE) -- Treadwell Therapeutics, a clinical-stage biotechnology company developing novel first-in-class medicines for unmet needs in cancer, today announced a presentation for the Company's lead program, CFI-400945, a first-in-class inhibitor of Polo-like Kinase 4 (PLK4) being advanced in relapsed/refractory AML, at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition being held from December 9-12, 2023. Treadwell also conducted a clinical advisory board meeting on December 10th at ASH with experienced experts in the treatment of AML and in clinical trials of novel agents, which included current investigators and thought leaders new to the program. "CFI-400945 is demonstrating complete remissions as a single agent and in combination with azacitadine in relapsed, adverse risk AML, including those with TP53 mutant disease. As we optimize dose and schedule, we are encouraged by the data with this oral dosing regimen," said Principal Investigator and Advisory Board Co-Chair Dr. Gautam Borthakur, MD, Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The advisory board confirmed the enthusiasm about the data to date in the relapsed AML setting, in particular with TP53 mutant disease and look forward to working with Treadwell to advance and shape this program.” "CFI-400945, our lead program and first-in-class PLK4 inhibitor, represents an opportunity to address a substantial unmet in relapsed/refractory AML, including TP53 mutant AML," said Roger Sidhu, MD, Acting CEO at Treadwell Therapeutics. “We look forward to advancing the program into key dose expansion studies in monotherapy and in combination in 2024 with a view to initiating pivotal studies in 2025.” 2023 ASH Poster Presentations and Details: Title: Preliminary Results from a Phase 1b/2 Open-Label, Multicenter, Dose Optimization Clinical Study of the Safety, Tolerability, and Pharmacokinetic (PK) and Pharmacodynamic (PD) Profiles of CFI-400945 As a Single Agent or in Combination with Azacitidine in Patients (Pts) with Acute Myeloid Leukemia, Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (TWT-202) Session Name: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III Publication Number: 4294 Session Date: Monday, December 11, 2023 Presentation Time: 6:00 PM - 8:00 PM Location: San Diego Convention Center, Halls G-H CFI-400945 has been generally well tolerated in this difficult to treat patient population, including patients whose disease has progressed on or following venetoclax based therapies. Three of 6 evaluable patients with AML achieved a response (MLFS=2, CRi=1 with MRD+) at the 96mg dose. After this data cut, one additional MLFS response (end of cycle 1) and two additional CRs (end of cycle 2) were seen in two patients treated with 80 mg + azacitidine combination cohort and became transplant eligible (PI communication). PK characteristics support daily dosing of CFI-400945 and PD studies are ongoing. Dose expansions are planned and enrollment continues. About Treadwell Therapeutics Treadwell Therapeutics is a clinical-stage oncology company developing novel medicines to address unmet needs in patients with cancer. The Company's robust, internally developed clinical pipeline includes CFI-400945 (PLK4 inhibitor), CFI-402257 (TTK/Mps1 inhibitor) and CFI-402411 (HPK1 inhibitor). Treadwell also has a broad pre-clinical pipeline with multiple biologic and next generation TCR based autologous cell therapy programs. For more information, please visit Contact ir@treadwelltx.com

Clinical ResultASHCell TherapyImmunotherapyAACR

06 Dec 2023

·www.biospace.com

Treadwell Announces Strategic Pipeline Prioritization and Leadership Transitions

– Treadwell to focus on advancing first-in-class PLK4 inhibitor CFI-400945 in AML towards potential pivotal studies in 2025 – Approximately 30% reduction in workforce to extend cash runway – Roger Sidhu, M.D. appointed as Acting CEO replacing founding Co-CEOs, Shane Burgess and Michael Tusche, Ph.D., Shane Burgess to transition to Executive Chair TORONTO and SAN FRANCISCO, Dec. 06, 2023 (GLOBE NEWSWIRE) -- Treadwell Therapeutics, a clinical-stage biotechnology company developing novel first-in-class medicines for unmet needs in cancer, today announced that it is realigning its pipeline, workforce and management structure to support its highest value program and extend its cash runway to prioritize the execution of key near term value drivers and clinical milestones. Treadwell has elected to focus on its first-in-class PLK4 inhibitor, CFI-400945, in relapsed/refractory AML by expanding the ongoing company sponsored TWT-202 study, building on exciting signals of efficacy seen at earlier phases, and advancing towards a potential pivotal study in 2025. The company will seek to capitalize on very promising proof-of-concept from sponsored clinical studies of CFI-402257 (TTK/Mps1 inhibitor) and CFI-402411 (HPK1 inhibitor) through further, innovative collaborative studies and work with potential partners to accelerate timelines. Shane Burgess, co-CEO has transitioned to the role of Executive Chair, while Michael Tusche, Ph.D., co-CEO has left the company to pursue other endeavours. Roger Sidhu, M.D., Chief Medical Officer, has been appointed Acting CEO. Dr. Sidhu brings to Treadwell an extensive track record of success over the last nearly 20 years in hematologic and solid tumor oncology research and development. He is a seasoned leader with deep translational, clinical and regulatory experience across multiple therapeutic modalities and platforms including small molecules, biologics and cell and gene therapies. Most recently, Dr. Sidhu was the Chief Medical Officer at Eterna Therapeutics, a gene editing and cell therapy company where he advanced multiple novel programs. Previously, Dr. Sidhu served as Executive Vice President and Chief Medical officer at Roivant Sciences. Roger was also the Chief Medical Officer at Cell Design Labs, up until its acquisition by the Gilead subsidiary Kite, where he subsequently served as VP, Clinical Development. Dr. Sidhu also held various roles of increasing responsibility at Amgen over a nearly decade that included managing FDA and EU approval of panitumumab in metastatic colorectal cancer. Dr. Sidhu is a Fellow of the Royal College of Physicians and Surgeons of Canada in both internal medicine and medical oncology. He earned his medical degree from Queen's University in Kingston, Ontario Canada. “Roger brings a unique and broad set of skills and strategic thinking to Treadwell over a long and successful career. We are confident that under his leadership, Treadwell will aggressively advance into an exciting new chapter in our mission to address unmet needs in difficult to treat cancers with first-in-class medicines,” said Shane Burgess, Executive Chair of Treadwell Therapeutics. “In order to increase operational efficiency and to focus on key, value driving priorities, we have made the difficult business decision to reduce our workforce by approximately 30% and to redirect clinical efforts for several Treadwell-sponsored trials to other avenues. We would like to extend our deep gratitude to the Treadwell team, investigators and patients involved in our clinical programs. These actions allow us to focus on investing in key near term milestones for CFI-400945.” “Treadwell has developed a broad clinical and research-stage pipeline of first-in-class small molecules, biologics and TCR-based cell therapies. We have reached an inflection point which allows us to focus on the most near-term path to value with CFI-400945 in relapsed/refractory AML with a view to advancing to pivotal stage studies,” said Roger Sidhu, M.D., Acting CEO of Treadwell Therapeutics. “Given the very promising clinical data we have generated, we also look forward to advancing CFI-402257 (TTK inhibitor) and CFI-402411 (HPK1 inhibitor) with external collaborators and investigators moving forward in breast cancer and immunotherapy-based treatment of cancer, respectively, in addition to actively seeking partners for our pre-clinical programs.” About Treadwell Therapeutics Treadwell Therapeutics is a clinical-stage oncology company developing novel medicines to address unmet needs in patients with cancer. The Company's robust, internally developed clinical pipeline includes CFI-400945 (PLK4 inhibitor), CFI-402257 (TTK/Mps1 inhibitor) and CFI-402411 (HPK1 inhibitor). Treadwell also has a broad pre-clinical pipeline with multiple biologic and next generation TCR based autologous cell therapy programs. For more information, please visit . Contact ir@treadwelltx.com

Executive ChangeGene TherapyCell TherapyImmunotherapy

100 Deals associated with CFI-402257

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	United States	Treadwell Therapeutics, Inc.	27 May 2022
ER-positive/HER2-negative Breast Cancer	Phase 2	United States	Treadwell Therapeutics, Inc.	27 May 2022
Breast Cancer	Phase 2	-	University Health Network	-
Acute Myeloid Leukemia	Discovery	Canada	Treadwell Therapeutics Canada, Inc.	07 Dec 2024
Acute Myeloid Leukemia	Discovery	Hong Kong	The University of Hong Kong	07 Dec 2024

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03568422 (CTgov)	Phase 1/2	HER2-negative breast cancer	37	Paclitaxel+CFI-402257	ameillaksz = vawmitrdye jhygenmxyn (isgtgvurkj, ircymtoxan - cnjiruikfy)	-	26 Jun 2024
SABCS2023	Phase 1	HER2-negative breast cancer ER+ \| TNBC \| RB1 loss	87	CFI-402257 monotherapy	rxcpyluync(mwgetfhyxp) = vniqymbyuy luhdolvlye (bskwhkniek ) View more	Positive	01 Mar 2023
				CFI-402257 in combination with Fulvestrant	qsbxayhoct(kmdkroffky) = jahynwtusn qjwpfrzxut (ezdexokfin )
SABCS2023	Phase 1	HER2-negative breast cancer HER2-negative	37	CFI-402257	iusqcunvky(aiyhopfnbd) = Frequent AEs (>5%; all dose levels) considered at least possibly related to treatment were: alopecia (11%) ynzxvuesrf (tbmgnisuqz ) View more	Positive	01 Mar 2023
				Paclitaxel
NCT05251714 (TWT-203, ASCO2022)	Phase 1/2	HR-positive/HER2-low Solid Tumors \| ER-positive/HER2-negative Breast Cancer	-	CFI-402257 monotherapy	frsaasfqdn(sjqifsndsq) = Safety endpoints include incidence of treatment emergent adverse events alsxyuvwwt (adukwbahfh )	-	02 Jun 2022
P1-18-17 (SABCS2022)	Phase 1	Advanced breast cancer ER+ \| HER2- \| TNBC ... View more	66	CFI-402257 5mg	msjmwvpdzb(axcwxicphh) = iptuulsqww sboebihtbe (wxsdkhcerq ) View more	Positive	15 Feb 2022
				CFI-402257 168mg	whmqeunfvm(efullmbppo) = lmnzowdyak xizvffdewt (fxjzmbcwpw ) View more

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