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

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

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

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

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

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

Ixabepilone in Treating Participants With Significant Residual Disease of HER2/Neu Negative Invasive Breast Cancer After Systemic Therapy (clinicaltrials.gov) - P2 | N=116 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • CTCs • HER-2

Randomized phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer (NCT03093155): Updated survival and subgroup analyses. (PubMed, BJC Rep) - P2 | "IXA + BEV has activity in heavily pre-treated ovarian cancers and offers significant improvement in ORR and PFS/OS compared to IXA, despite prior taxane response and dose reductions."

Journal • P2 data • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Ixabepilone-Induced Delirium. (PubMed, Am J Ther) - No abstract available

Journal • CNS Disorders

Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy (clinicaltrials.gov) - P=N/A | N=5 | Terminated | Sponsor: 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

Biomarker • Biopsy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Oncology • Solid Tumor

Total Synthesis of an Epothilone Analogue based on the Amide‒Triazole Bioisosterism. (PubMed, Chempluschem) - "A notable exception is Ixabepilone, an azalide representing the only epothilone-like molecule approved by the FDA as a chemotherapeutic. Exploiting the amide-triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too."

Journal • Oncology

Anti-tumor Effect of Ixabepilone in Metastatic Breast Cancer (mBC) Selected by the Ixabepilone DRP. (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Allarity Therapeutics | Trial primary completion date: Jun 2024 ➔ Sep 2024

Metastases • Trial primary completion date • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Microtubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy. (PubMed, Adv Exp Med Biol) - "Unfortunately, the development of resistance continues to present a therapeutic challenge. An understanding of the underlying mechanisms of resistance to microtubule-active agents may facilitate the development of novel and improved approaches to this disease."

Journal • Review • Oncology • Ovarian Cancer • Solid Tumor

Ixabepilone related angiographically silent macular edema. (PubMed, Eur J Ophthalmol) - "Angiographically silent intraretinal cystoid changes may develop in association with the use of ixabepilone. Referral to an ophthalmologist should be considered for the patients experiencing visual complaints as ixabepilone cessation may lead to visual improvement and avoid unnecessary treatment."

Journal • Breast Cancer • Cataract • Glaucoma • Macular Degeneration • Macular Edema • Oncology • Ophthalmology • Retinal Disorders • 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)

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

Randomized phase II trial of weekly ixabepilone with or without biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer: Updated survival and subgroup analyses (SGO 2024) - P2 | "Patients were considered ‘taxane-resistant’ if they had demonstrated disease progression within 6 months of paclitaxel/docetaxel administration and ‘taxane-refractory’ if they progressed while receiving a taxane or demonstrated persistence of disease on end-of treatment assessment that prompted initiation of a new line of therapy. The combination of IXA+BEV has activity in heavily pre-treated ovarian cancers, and offers significant improvement in ORR, PFS and OS compared to IXA alone, regardless of prior taxane response and even in the setting of dose reductions. Additional molecular studies are warranted to identify predictors of durable response."

Clinical • P2 data • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer