Ixempra (ixabepilone) / Otsuka, BMS, R-Pharm, Allarity Therap - LARVOL DELTA

Association of tumor infiltrating lymphocyte quantity with survival in patients (pts) with metastatic breast cancer (MBC) receiving microtubule-targeting agents: Post hoc analysis CALGB 40502 (Alliance). (ASCO 2023) - P3 | "CALGB (Alliance) 40502 was a randomized phase 3 trial of 799 MBC pts receiving first-line chemotherapy, comparing paclitaxel, nab-paclitaxel or ixabepilone with or without bevacizumab. Immune activation measured by sTILs is significantly lower in met tumors than primary breast cancer and varies by met site. In this trial, sTILs were associated with progression-free and overall survival in chemotherapy-treated MBC, with a trend toward independent value adjusted for other prognostic features. Clinical trial information: NCT00785291."

Clinical • Metastases • Retrospective data • Tumor-infiltrating lymphocyte • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor

Treatment With Etirinotecan Pegol for Patients With Metastatic Breast Cancer and Brain Metastases: Final Results From the Phase 3 ATTAIN Randomized Clinical Trial. (PubMed, JAMA Oncol) - P3 | "Patients were randomized to receive etirinotecan pegol, 145 mg/m2, every 21 days or chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). However, this study represents one of the largest published trials dedicated to patients with breast cancer and BM and may help to inform further research. ClinicalTrials.gov Identifier: NCT02915744."

Clinical • Journal • P3 data • Breast Cancer • Oncology • Solid Tumor

Whole-Exome Sequencing Identifies Candidate Genomic Features Associated with Response to Platinum-Based Chemotherapy and Ixabepilone-Based Treatment in Ovarian Cancer. (PubMed, Int J Mol Sci) - "Carboplatin/paclitaxel (CP) chemotherapy is the cornerstone of therapy for advanced stage ovarian cancer (OC)...Ixabepilone ± bevacizumab (IB) is a combination recently added to NCCN guidelines for the treatment of platinum-resistant OC...Alterations in genes associated with tumor growth/progression correlated with resistance to CP regimen and may represent novel "druggable" candidate biomarkers for the targeted treatment of CP/IB-resistant patients. Further validation in independent cohorts and preclinical experiments in CP/IB-resistant models are warranted to establish the clinical utility of these findings."

Biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • ACVR2A • ATG5 • LRRK2 • MAP3K7 • RSPO3 • SDHA

ESR1 hotspot–specific chemotherapy resistance patterns in metastatic breast cancer identified by ctDNA analysis. (ASCO 2026) - "The cases sensitive vs resistant to chemotherapy drugs are as follows: Doxorubicin (22 vs 18), Epirubicin (33 vs 7), Pegylated Liposomal doxorubicin (37 vs 3), Carboplatin (25 vs 15), Paclitaxel (21 vs 19), Docetaxel (23 vs 17), Vinorelbine (29 vs 11) , Ixabepilone (34 vs 6), Eribulin (32 vs 8), Capecitabine (17 vs 23), Cyclophosphamide (16 vs 24), Gemcitabine (36 vs 4), and Abraxane (35 vs 5). Our findings indicate that baseline ctDNA ESR1 hotspot heterogeneity is associated with distinct chemotherapy resistance patterns. Non-classic ESR1 hotspots were enriched for vinorelbine resistance, whereas D538G was inversely associated with an extreme multi-drug resistance phenotype (≥5 agents), suggesting ESR1 hotspots may serve as a clinically relevant biomarker for chemotherapy resistance spectrum, supporting prospective validation and biomarker-guided treatment strategies."

Circulating tumor DNA • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer (clinicaltrials.gov) - P2 | N=349 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer • AKT1

ESR1 mutations in circulating tumor DNA (ctDNA) are significant predictors of chemotherapy resistance to paclitaxel and carboplatin in metastatic breast cancer (MBC) (AACR 2025) - "The numbers of cases sensitive vs resistant to chemotherapy along with the corresponding drugs are as follows: Doxorubicin (22 vs 18), Epirubicin (33 vs 7), Pegylated Liposomal doxorubicin (37 vs 3), Carboplatin (25 vs 15), Paclitaxel (21 vs 19), Docetaxel (23 vs 17), Vinorelbine (29 vs 11) , Ixabepilone (34 vs 6), Eribulin (32 vs 8), Capecitabine (17 vs 23), Cyclophosphamide (16 vs 24), Gemcitabine (36 vs 4), and Nab paclitaxel (35 vs 5). These findings demonstrate for the first time that ctDNA ESR1 mutations are associated with chemotherapy resistance to both Carboplatin and Paclitaxel. Such mutations contribute to tumor heterogeneity, enabling mutated receptors to support tumor survival despite cytotoxic treatment. Detecting ESR1 mutations in MBC may serve as a consideration for guiding chemotherapy decisions and exploring alternative therapeutics."

Circulating tumor DNA • Metastases • Breast Cancer • Oncology • Solid Tumor • ER

Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2026 ➔ Mar 2027

Trial completion date • Oncology • Solid Tumor

Folic acid-targeted chitosan-alginate blend nanoparticles for enhanced ixabepilone delivery and antitumor efficacy in breast cancer. (PubMed, Int J Biol Macromol) - "Folic acid-mediated targeting improved tumor accumulation, biodistribution, and therapeutic efficacy, as supported by IVIS imaging. Overall, this blended nanoparticle platform represents a formulation approach for targeted IXA delivery and shows potential for further investigation in breast cancer models."

Journal • Breast Cancer • Oncology • Solid Tumor

Anti-tumor Effect of Ixabepilone in Metastatic Breast Cancer (mBC) Selected by the Ixabepilone DRP. (clinicaltrials.gov) - P2 | N=13 | Terminated | Sponsor: Allarity Therapeutics | N=60 ➔ 13 | Suspended ➔ Terminated; Company Decision

Enrollment change • Trial termination • Breast Cancer • Oncology • Solid Tumor

Folic acid-conjugated biopolymeric nanoparticles for targeted delivery of ixabepilone in breast cancer. (PubMed, Prep Biochem Biotechnol) - "Cytotoxicity studies on MDA-MB-231 and MCF-7 breast cancer cell lines revealed enhanced cytotoxic effects of FA-conjugated IXA-loaded NPs in FR-positive MDA-MB-231 cells compared to MCF-7 cells, suggesting preferential FR-mediated cellular interaction. Overall, FA-functionalized CS and ALG NPs represent a promising in vitro platform for targeted IXA delivery in FR-expressing breast cancer therapy."

Journal • Breast Cancer • Oncology • Solid Tumor

Meta-Analysis and Experimental Studies Reveal Mitotic Network Activity Index (MNAI) as Breast Cancer Metastasis and Treatment Biomarker. (PubMed, Life (Basel)) - "Moreover, BC cells with high MNAI increased sensitivity to microtubule-targeting agents such as docetaxel, paclitaxel, and ixabepilone but increased resistance to tamoxifen, AKT1/2 inhibitors, and mTOR inhibitors. Consistent with these findings, analysis of 16 clinical trial cohorts revealed that patients with high MNAI achieved higher pathological complete response rates to taxane-containing and ixabepilone-based therapies. Our findings demonstrate the MNAI as a clinically actionable biomarker that can refine risk stratification and guide the selection of targeted or chemotherapy regimens, advancing precision medicine in BC management."

Biomarker • Journal • Retrospective data • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AKT1 • BUB1 • CHEK1 • ER • PLK1

Rna-based immune features associated with benefit from distinct microtubule inhibitor therapy for metastatic her2-negative breast cancer: a post hoc analysis of the calgb 40502 (alliance) phase iii randomized clinical trial (SABCS 2025) - P3 | "CALGB (Alliance) 40502 was a phase 3 randomized study involving 799 patients with MBC receiving first-line chemotherapy, to determine the optimal chemotherapeutic agent among paclitaxel, nab-paclitaxel, or ixabepilone (with or without bevacizumab). In this translational analysis of sTILs and RNAseq from a large phase III clinical trial, sTILs and immune signatures were not uniformly associated with better outcome. Rather, high sTILs or immune signatures were associated with worse OS in young patients with HR+/HER2- breast cancer and higher T-cell signatures were associated with inferior PFS with nab-paclitaxel among HR+/HER2- MBC patients. These data reinforce the importance of context/subtype-specific interrogation of the tumor-immune microenvironment.Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org."

Clinical • Metastases • P3 data • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Defining a Neuroinflammatory Signature of Chemotherapy-Induced Peripheral Neuropathy (SABCS 2025) - " This cohort consists of 14 pts with metastatic breast cancer enrolled in a phase 2 study of ixabepilone in which the primary endpoint of the original trial was to define the effect of ixabepilone on the development of CIPN and on the ultrastructure of neurons evaluated by electron microscopy of serial skin biopsies... Together, these seven biomarkers reveal a novel neuroinflammatory signature of CIPN. Elevated serum levels of CCL18 and PDGF-AA in patients with severe CIPN are suggestive of chemotherapy-induced pro-fibrotic macrophage activation, which has been shown to exacerbate neuropathy. While CCL8 and CCL23 have been reported in the literature in relation to peripheral neuropathy, this study marks the first report identifying CCL24 in this context."

Breast Cancer • CCL18 • CCL23 • CCL8 • CCR3 • IL12A

Unveiling the Unlikely: Stercoral Colitis Masking Rare Breast Metastasis: A Case Report (ACG 2025) - "This case underscores the challenges in distinguishing between primary gastrointestinal issues and metastatic disease in breast cancer patients.Case Description/ An 84-year-old woman with a history of coronary artery disease, currently on clopidogrel and aspirin, also had stage II invasive ductal carcinoma with extensive lymph node involvement...After poorly tolerating hormonal treatment, she faced a recurrence of cancer in the neck, treated with CyberKnife therapy, radiotherapy, and brief Ixempra chemotherapy until 2012...Given the poor prognosis associated with GI metastasis, treatment strategies focus on palliative care, including hormonal therapy for receptor-positive cases and interventions to alleviate obstruction. Overall survival after diagnosis ranges from 4.7 to 33 months, with a median survival of 33 months observed in a specific cohort.Figure: Figure 1 - Stercoral colitis on colonoscopyFigure: Figure 2 - Stercoral biopsy results indicating metastatic breast..."

Case report • Clinical • Anemia • Breast Cancer • Colorectal Cancer • Coronary Artery Disease • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • HER2 Positive Breast Cancer • Immunology • Palliative care • Solid Tumor • CDX2 • GATA3 • HER-2 • Mammaglobin • PGR • SCGB2A2

Predicting and Optimizing Synergistic Drug Combinations for Breast Cancer Treatment Using Machine Learning. (PubMed, Am J Clin Oncol) - "The study demonstrates the effectiveness of machine learning in predicting synergistic drug combinations for breast cancer. By accelerating the screening process and reducing experimental burden, the approach offers a promising tool for guiding future in vitro and in vivo validation of combination therapies."

Journal • Breast Cancer • Oncology • Solid Tumor

Integrating Multiomics and Machine Learning: Senescence-Regulated ALMS1-IT1/miR-7c-5p/HMGA2 Axis as a Novel Therapeutic Target for Head and Neck Squamous Cell Carcinoma. (PubMed, ACS Omega) - "Single-cell analysis of dysregulated expression within the ALMS1-IT1/miR-7c-5p/HMGA2 axis predominantly highlighted aberrant interactions between immune cells and epithelial cells. Drug sensitivity evaluations suggested that inhibitors targeting ALMS1-IT1, such as sulforaphane and cloxacillin, alongside HMGA2 inhibitors such as ixabepilone, provide innovative, personalized, and combined targeted therapeutic strategies for patients with HNSCC."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HMGA2

Genomic profiling of a collection of patient-derived xenografts and cell lines identified ixabepilone as an active drug against chemo-resistant osteosarcoma. (PubMed, J Exp Clin Cancer Res) - No abstract available

Journal • Preclinical • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer (clinicaltrials.gov) - P2 | N=349 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer • AKT1

Clinical Manifestations of Neuropathic Pain and the Deleterious Effects of Chemotherapeutic Agents. (PubMed, Curr Drug Saf) - "A variety of chemotherapeutic agents can contribute to the development of CIPN, including vinca alkaloids, platinum-based antineoplastic agents, epothilones (ixabepilone), proteasome inhibitors (bortezomib), taxanes, and immunomodulatory drugs (thalidomide), along with the genetic factors...Pharmacological interventions, such as anticonvulsants, gabapentin, and pregabalin, are commonly used to manage neuropathic pain. Tricyclic antidepressants like amitriptyline and nortriptyline can be effective, but their use may be limited due to side effects...The lidocaine or capsaicin creams and patches can provide localized pain relief...Transcutaneous electrical nerve stimulation and spinal cord stimulation are invasive procedures that may be considered for severe, intractable pain. Complementary therapies and cognitive-behavioural therapy can help patients cope with pain and improve their quality of life."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Neuralgia • Oncology • Pain • Psychiatry • CEP72

Ixabepilone and Temsirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Oncology • Solid Tumor

Anti-tumor Effect of Ixabepilone in Metastatic Breast Cancer (mBC) Selected by the Ixabepilone DRP. (clinicaltrials.gov) - P2 | N=60 | Suspended | Sponsor: Allarity Therapeutics | Recruiting ➔ Suspended

Trial suspension • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Single-cell transcriptomics analysis reveals dynamic changes and prognostic signature in tumor microenvironment of PDAC. (PubMed, Sci Rep) - "Furthermore, our analysis revealed significant interactions between cells at different stages of PDAC and identified three promising therapeutic agents (XR-11576, Ixabepilone, and AMONAFIDE) based on correlated genes. Finally, molecular docking studies validated their potential by confirming stable binding with key protein targets. This study not only provides insights into the evolving TME of PDAC but also offers a new prognostic model and potential therapeutic strategies, contributing to improved management and treatment of this aggressive cancer."

Biomarker • IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CTSD • FCGR2A • HMOX1 • HSPB1 • IFI30 • NPC2 • SEC61G • TNFRSF4 • ZFP36 • ZFP36L1

Evaluation of ixabepilone efficacy and tolerability in metastatic breast cancer. (PubMed, Medicine (Baltimore)) - "In our study, we showed that ixabepilone treatment has a statistically significant positive effect on survival if preferred in earlier metastatic lines. As similar studies increase in centers where ixabepilone treatment is generally given in advanced metastatic lines, treatment approaches may change in the coming years."

Journal • Retrospective data • Breast Cancer • Oncology • Solid Tumor

Convergent Total Synthesis of Ixabepilone and Its Analogues Enabled by Highly Efficient Asymmetric Hydrogenations. (PubMed, Chemistry) - "The key aldol reaction bridges the aldehyde and keto fragments with high yield and exquisite diastereo control (8:1 d.r.). Finally, a novel RCM reaction conformationally controlled by a bulky silyl group was reported, which allows the facile synthesis of ixabepilone and its analogues."

Journal

Targeted and cytotoxic inhibitors used in the treatment of breast cancer. (PubMed, Pharmacol Res) - "Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and..."

IO biomarker • Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • HER-2 • PGR • PIK3CA