Ixempra (ixabepilone)

P=N/A, N=5, Terminated, University of Wisconsin, Madison | N=35 --> 5 | Trial completion date: Aug 2024 --> Feb 2024 | Recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Feb 2024; slow accrual

P2, N=60, Recruiting, Allarity Therapeutics | Trial primary completion date: Jun 2024 --> Sep 2024

P2, N=349, Active, not recruiting, National Cancer Institute (NCI)

P1, N=22, Active, not recruiting, National Cancer Institute (NCI)

In addition, GSE173839, GSE25066, GSE41998, and GSE194040 dataset analyses of the underlying CCC signature suggested that durvalumab with olaparib and paclitaxel, taxane-anthracycline chemotherapy, neoadjuvant cyclophosphamide/doxorubicin with ixabepilone or paclitaxel, and immunotherapeutic strategies might be suitable for COAD patients with higher CCC score. Eventually, the GDSC database analysis showed that lower CCC scores were likely to be more sensitive to 5-fluorouracil, bosutinib, gemcitabine, gefitinib, methotrexate, mitomycin C, and temozolomide, while patients with higher CCC score seemed to have a higher level of sensitivity to bortezomib and elesclomol. The novel CCC signature exhibited a good ability for prognosis prediction for COAD patients, and the CCC score was found to be highly correlated with molecular features, immune-related characteristics, and therapeutic responses, which would greatly promote clinical management and precision medicine for COAD.

P2, N=60, Recruiting, Allarity Therapeutics | Trial primary completion date: Nov 2023 --> Jun 2024

P2, N=78, Completed, Yale University | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Dec 2022

"Allarity Therapeutics, Inc...is pleased to announce that the Company has been invited to give a presentation at Biomarkers Europe 2023. The presentation will focus on Allarity’s development of drug-specific DRP^® companion diagnostics (CDx) for oncology therapeutics, featuring clinical validation for several exemplary DRP^® CDx....In addition to its presentation, Allarity is honored to participate in a panel discussion titled 'Prediction Of Drug Response Using An Ex Vivo Organ Culture (EVOC) On Oncology Patients, Clinical Trial Development And Patient Testing' at the same conference."

P2 | N=176 | NCT00593827 | Sponsor: R-Pharm | "Allarity Therapeutics, Inc...announced initial results from its European Phase 2 clinical trial evaluating the efficacy of IXEMPRA^® in metastatic breast cancer (mBC) patients selected with the DRP^®-IXEMPRA^® companion diagnostic (CDx) candidate....Among the evaluable patients assessed up to the data evaluation cut-off, there were promising signs of clinical benefit in four out of four evaluable cases: One partial responder (PR) (tumor shrinkage of 66%). One partial responder (PR) (tumor shrinkage of 59%). One patient experienced 24 weeks of stable disease. One patient experienced 19 weeks of stable disease....The Company anticipates an additional interim data readout before the end of this year."

Small-molecule drugs panobinostat, oxaliplatin, ixabepilone, and seliciclib were significantly associated with ADH1B. Our study provides ADH1B as a key afatinib-related gene, which is associated with the immune microenvironment and can be used to predict the prognosis of LIHC. It is also a potential target of candidate drugs, sharing a promising approach to the development of novel drugs for the treatment of LIHC.

Today, there are many medical applications for compounds containing the thiazole moiety owing to their presence in most clinically applied anticancer drugs, such as dasatinib, dabrafenib, ixabepilone, patellamide A and epothilone. It was clear that there was an enhancement in the anticancer activity for the synthesized polyamides owing to the presence of the thiazole moiety as well as sulfur linkage. According to the results of the 50% inhibitory concentration (IC50), the synthesized polymers were found to be more active against the MCF-7 cell line than the HCT cell line.

P=N/A, N=35, Recruiting, University of Wisconsin, Madison | Trial completion date: Aug 2023 --> Aug 2024 | Trial primary completion date: Jun 2023 --> Jun 2024

P2, N=0, Withdrawn, Jenny C. Chang, MD | N=14 --> 0 | Terminated --> Withdrawn

The overall survival, disease-free survival, relapse-free survival, distant metastasis-free survival, and the complete pathological response of TNBC patients with high expression of BIRC5 who received any chemotherapy (Taxane, Ixabepilone, FAC, CMF, FEC, Anthracycline) and anti-HER2 therapy (Trastuzumab, Lapatinib) did not differ significantly from those patients receiving any other treatment. Meanwhile, several in vitro studies show that flavonoids were highly effective in inhibiting BIRC5 in genetically diverse TNBC cells. Therefore, flavonoids would be a promising strategy for preventing and treating TNBC patients with the BIRC5 molecule.

These findings suggest that the ixabepilone/vandetanib combination may have promise for the treatment of patients with drug-resistant TNBC.

Models ST4887 and ST4887B were established from metastatic samples collected from a Caucasian female with ER+/HER2- metastatic breast cancer; ST4887 was collected at age 38 from a femur mass biopsy following several treatment regimens including paclitaxel/doxorubicin/cyclophosphamide, radiation and tamoxifen. ST4887B was collected at age 39 from a liver biopsy following treatment with palbociclib/letrozole then palbociclib/fulvestrant, and finally ixabepilone/capecitabine...For in vivo studies, both models were evaluated using several chemotherapy and targeted agents alone and in combination including cisplatin, docetaxel, CDK4/6i, fulvestrant, letrozole, olaparib, niraparib, and sacituzumab...In vivo, both models were insensitive to cisplatin or docetaxel, however ST4887 but not ST4887B was sensitive to fulvestrant or CDK4/6i therapies, although abemaciclib demonstrated some activity toward ST4887B... We established and characterized two XPDX models from the same patient before and after acquired resistance to the CDK4/6i palbociclib. Both models were found to retain receptor status and drug sensitivities similar to the patient at the time of sample collection. These models can be utilized as a valuable tool in better understanding acquired resistance to palbociclib.

P3, N=799, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

As single agents, the VEGFR inhibitors cediranib and bosutinib decreased both 231C and TXT cell viability, but four other VEGFR inhibitors and two PARP inhibitors were less effective. Thus, TXT cell killing by ixabepilone/cediranib was enhanced over ixabepilone alone, and expression of proapoptotic cleaved caspase-3 and the Bak/Bcl-2 protein ratio were increased. These findings suggest that the synergistic activity of the ixabepilone/cediranib combination in taxane-sensitive and taxane-resistant cells may warrant clinical evaluation in TNBC patients.

P2, N=78, Active, not recruiting, Yale University | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Feb 2022 --> Feb 2023

Pharmaceutical regimens based on two natural compounds, trabectedin and ixabepilone, have been investigated in humans showing short and midterm efficacy as second-line treatments in phase II clinical trials. The purpose of this review is twofold: the authors first provide an overview of the involvement of kinases and kinase inhibitors in the pathogenesis and treatment of EC and then discuss the existing evidence about natural products' derived kinase inhibitors in the management of the disease and outline relevant future research.

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Dec 2021 --> Dec 2022

IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker.

PTPRT might be primary resistance biomarkers for taxane, anthracycline, and ixabepilone but not be acquired resistance biomarkers...PTPRT could predict chemotherapy effectiveness and prognosis for breast cancer patients. PTPRT might inhibit tumor growth via disrupting the microtubule dynamics and cell cycle in breast cancer.

Our findings confirm that this data-driven systems pharmacogenomics strategy is a powerful approach for the discovery and validation of novel therapeutic candidates relevant to MB treatment, and along with data validating ixabepilone in PDX models of the two most aggressive subtypes of medulloblastoma, we present the network analysis framework as a resource for the field.

P3, N=762, Completed, UNICANCER | Active, not recruiting --> Completed | Trial completion date: Sep 2019 --> Sep 2020

P2, N=116, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2020 --> Dec 2022 | Trial primary completion date: Apr 2020 --> Dec 2021

In the current study, we determined the concentration and time-dependent effects of paclitaxel, docetaxel, ixabepilone, eribulin, and vinorelbine on the cytokine expression profiles in both immune and TNBC cells. Together, these results provide evidence that different MTAs have distinct immunomodulatory properties and highlight the ability of eribulin to promote the release of mtDNA to activate the cGAS-STING pathway, which has been previously shown to enhance the efficacy of immunotherapy in TNBC. These studies were funded by Eisai.

P3, N=178, Completed, Nektar Therapeutics | Active, not recruiting --> Completed | Trial completion date: Mar 2021 --> Jul 2020

Prediction results revealed that Ixabepilone, an epothilone B analog for treating breast cancer patients, may target Bcl-2, an oncogene that contributes to tumor progression and therapy resistance by inhibiting apoptosis. In addition, Ixabepilone also decreases Bcl-2 protein expression and induces cytoprotective autophagy in human hepatic carcinoma and glioma cells. In conclusion, this study not only provides a feasible and alternative way exploring new molecular mechanisms of drugs by combing computation DTI prediction, but also reveals an effective strategy to reinforce the antitumor efficacy of Ixabepilone.

Recently, the combination of the PD-L1 inhibitor atezolizumab with the taxane nab-paclitaxel was found to prolong progression-free survival in patients with metastatic TNBC...The effects of 5 MTAs used for the treatment of TNBC, paclitaxel, docetaxel, ixabepilone, vinorelbine, and eribulin, on the expression of antitumor cytokines and other immunomodulatory genes in myeloid and TNBC cells was evaluated...Together, these results provide evidence that MTAs have different immune modulatory properties and suggest that the specific immune signatures initiated by different MTAs need to be considered for their optimal use with targeted agents, including checkpoint inhibitors. These studies were funded by Eisai.

P3, N=178, Active, not recruiting, Nektar Therapeutics | Recruiting --> Active, not recruiting

Most notably, the combination of the PD-L1 inhibitor atezolizumab with the taxane nab-paclitaxel was shown to prolong progression-free survival in patients with metastatic TNBC.3 Although it is known that paclitaxel can function as a TLR4 agonist leading to activation of the innate immune system, there has been little comparison of the immunogenic effects elicited by different clinically used MTAs for the treatment of TNBC. We evaluated the effects of 5 distinct MTAs used for the treatment of TNBC, paclitaxel, docetaxel, ixabepilone, vinorelbine, and eribulin, on the expression of antitumor cytokines and other immunomodulatory genes in myeloid and in TNBC cells...A nanoparticle-incorporated STING activator enhances antitumor immunity in PD-L1-insensitive models of triple-negative breast cancer. JCI Insight 3 , (2018).