alisertib (MLN8237) / Takeda, Puma - LARVOL DELTA

Synergistic effects of Aurora A and AKT inhibitors combined with radiation in colon cancer cells. (PubMed, Discov Oncol) - "The integration of Aurora A and AKT inhibitors with radiation therapy synergistically enhances anticancer effects by amplifying DNA damage, disrupting mitotic progression, and inducing apoptosis. This combination represents a promising strategy for overcoming treatment resistance in colon cancer."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

ALISCA-Breast1: A phase II study of ALISertib in combination with endocrine therapy in patients with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast CAncer (ESMO-BC 2025) - P2 | "Eligible patients are randomized 1:1:1 to alisertib 30, 40, or 50 mg orally bid on d1−3, 8–10, and 15–17 q28d, plus physician's choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in recurrent/metastatic setting or progressed upon in adjuvant setting; up to 50 patients will be randomized per arm in the USA and Europe. All biomarkers will be assessed centrally. The study will determine the optimal alisertib dose to combine with ET."

Clinical • Combination therapy • Metastases • P2 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 • HER-2

Targeting EMT-driven metastatic breast cancer with mitotic inhibitors (ESMO-BC 2025) - "These findings highlight the therapeutic potential of AURKA inhibitors for targeting hybrid EMT states present in CTCs and invasive regions of primary tumors, offering a strategy to combat metastatic disease and potentially transform current breast cancer treatment."

Metastases • Breast Cancer • Oncology • Solid Tumor • CDH1 • CDH2 • CTCs • FN1 • SNAI1 • VIM • ZEB1

Puma Biotechnology Reports First Quarter Financial Results (Businesswire) - "We anticipate the following key milestones over the next 12 months: (i) presentation of interim data from ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (H2 2025); and (ii) presentation of additional interim data from the ALI-4201/ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (H2 2025)."

P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Small Cell Lung Cancer

O 6-methylguanine DNA methyltransferase (MGMT) expression in U1242 glioblastoma cells enhances in vitro clonogenicity, tumor implantation in vivo, and sensitivity to alisertib-carboplatin combination treatment. (PubMed, Front Cell Neurosci) - "The action of the widely used antiglioma drug, temozolomide (TMZ), relies on its ability to methylate DNA guanine bases leading to DNA double strand breaks and apoptosis. We additionally show that the combination of the AURKA inhibitor alisertib and carboplatin selectively induces apoptosis in high MGMT expressing wildtype U1242 cells versus MGMT KO U1242 cells and extends survival of mice orthotopically implanted with wildtype U1242 cells. This or other platinum-based drug combinations may represent a potentially effective treatment approach to chemotherapy for GBM with MGMT promoter hypomethylation."

Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • MGMT

Alisertib impairs the stemness of hepatocellular carcinoma by inhibiting purine synthesis. (PubMed, J Biol Chem) - "This disruption markedly impaired tumor spheroid formation, migration, and invasion in vitro, while significantly suppressing tumor growth in vivo-effects reversible by the AKT agonist SC79. Our findings revealed a novel therapeutic strategy targeting purine metabolism through AURKA/AKT axis inhibition, effectively eliminating HCC-TRCs."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

ALISertib in combination with endocrine therapy in patients with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast cancer: The phase 2 ALISCA-Breast1 study. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06369285 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • Metastases • P2 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 • HER-2

Alisertib and Pembrolizumab for the Treatment of Patients With Rb-deficient Head and Neck Squamous Cell Cancer (clinicaltrials.gov) - P1/2 | N=24 | Terminated | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Terminated; <75% participation accrual

Trial termination • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Pharmacological blockade of AURKA and NOTCH3 oncogenic pathways to inhibit cancer cell plasticity in triple negative breast cancer (AACR 2025) - "TNBC cells were treated with Alisertib (AURKA inhibitor, 50nM) or AV353 (NOTCH3 inhibitor, 200ng). This study demonstrates that selective AURKA and NOTCH3 pharmacological blockade results in the inhibition of cancer cell plasticity that is linked to reduction of undruggable nuclear PD-L1 in TNBC cells. Our findings provide the strong preclinical rationale to develop novel clinical trials for patients with advanced TNBC that are refractory to chemotherapy and show limited response to FDA-approved ICIs."

IO biomarker • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKA • CD44 • CD8 • NOTCH3

Therapy-induced senescence promotes tumor immunosuppression in cholangiocarcinoma (AACR 2025) - "Mice were treated for two weeks with the potent senescence inducers, alisertib, etoposide, or doxorubicin...Both p16+ and p21+ cancer cells were increased in tumors from patients who have undergone cytotoxic therapy with gemcitabine/cisplatin (Gem/Cis)... we have demonstrated that senescent cancer cells accumulate in tumors from patients treated with standard-of-care therapy with Gem/Cis. Senescent cancer cells enhance the abundance and suppressive function of MDSCs via TRAIL. Thus, senolysis has the potential to rewire the TIME, and augment response to systemic therapy."

IO biomarker • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CD8 • CDKN1A • CDKN2A

Aurora-A inhibition sensitizes HPV-driven cancers to anti-CTLA-4 immunotherapy by modulating the tumor immune microenvironment (AACR 2025) - "Alisertib (Ali), an Aurora kinase A inhibitor, may sensitize these cancers to ICIs by inducing apoptosis and DNA damage...RNA-seq analysis shows that Ali drives immune responses, further amplified by anti-CTLA-4, promoting both immune and metabolic reprogramming. These findings suggest that combining Ali with ICI could overcome resistance and improve therapeutic outcomes in HPV-positive cancers."

IO biomarker • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • AURKA • CASP3 • CD4 • CD8 • IFNG • LAG3

A novel class of multitarget small molecule PI3K-CDK4/6-CDK9-AURAKA/B inhibitor harnesses Warburg effect against non-small cell lung cancer (AACR 2025) - "Here, we describe how LCI139 harnesses the Warburg effect to induce synthetic lethality in NSCLC. LCI139-sensitive (NCI-H1703) and resistant (NCI-H1781) human NSCLC cells, identified from prior IC50 experiments, were treated with LCI139 (0.25 and 0.5μM) or single agent inhibitors PI3Ki (BKM120), CDK4/6i (Ribociclib), CDK9i (AZD4573), and AURKAi (Alisertib). Multitarget inhibitor, LCI139 is uniquely designed to harness the Warburg effect to induce synthetic lethality in glycolysis-reliant NSCLC by 1) inducing metabolic stress (pAMPK), 2) lowering the threshold to metabolic stress response (FoxO3 stabilization), and 3) enhancing caspase-dependent cell death non-canonical Cas8 activation."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ANXA5 • BAX • BCL2 • BCL2L11 • CDK9 • SLC2A1

Exploiting Rb-deficiency: Dual inhibition of TRIP13 and Aurora A as a path to mitotic catastrophe (AACR 2025) - "Our previous research demonstrated that the combination of Aurora A inhibition using specific inhibitor alisertib and TRIP13 depletion induced synthetic lethality selectively in Rb-deficient cancer cells where the combination induced mitotic catastrophe...This is the first study to elucidate the mechanism behind the synthetic lethality of TRIP13 and Aurora A in Rb-deficient cancer cells. These findings may provide important insight into how to rationally design novel therapeutic strategies targeting mitotic regulators by harnessing the therapeutic vulnerability of Rb-deficient cancer cells."

Oncology • Solid Tumor • AURKA • CDK1 • GSDME • TRIP13

Combination therapy with alisertib enhances the anti-tumor immunity induced by a liver cancer vaccine. (PubMed, iScience) - "In liver orthotopic tumor models, the combination of pGPC3 vaccine and alisertib demonstrated potent therapeutic efficacy through CD8+ T cell responses. These results indicate that alisertib enhances the pGPC3 vaccine's therapeutic effect, offering a promising strategy for HCC treatment."

Journal • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKA • ITGAX

ALISertib in Combination With Endocrine Therapy in Patients With Hormone Receptor-Positive, HER2-Negative Recurrent or Metastatic Breast Cancer: the Phase 2 ALISCA-Breast1 Study (MBCC 2025) - P2 | "Eligible patients will be randomized 1:1:1 to alisertib 30 mg, 40 mg, or 50 mg orally twice daily on days 1 to 3, 8 to 10, and 15 to 17 every 28 days and combined with physician's choice of anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen not previously used in the recurrent or metastatic setting or progressed upon in the adjuvant setting. Tumor tissue will be centrally assessed for biomarkers, including but not limited to RB1, MYC, TP53, ESR1, PI3K/AKT pathway, HER2, and AURKA genomic alterations and/or expression levels. The study is expected to determine the optimal alisertib dose to combine with ET and may identify biomarker(s) that define patients deriving the greatest benefit from alisertib-containing therapy."

Clinical • Combination therapy • Metastases • P2 data • Anemia • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Infectious Disease • Leukopenia • Neutropenia • Oncology • Solid Tumor • ER • HER-2 • MYC • RB1

IMPACT OF AURORA KINASE PATHWAY INHIBITION IN PENILE SQUAMOUS CELL CARCINOMA PATIENT-DERIVED XENOGRAFT MODELS (AUA 2025) - "Alisertib is a well-tolerated novel therapy that induces a cytostatic effect on PSCC PDX models via Aurora kinase inhibition without tumor cell death. Further molecular characterization of alisertib treated tumors is in progress to better define strategies to induce apoptosis."

Preclinical • Genetic Disorders • Head and Neck Cancer • Immunology • Oncology • Penile Cancer • Primary Immunodeficiency • Rare Diseases • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CASP3

Degradation of N-Myc by HSP70 Inhibition Enhances the Effect of Alisertib in Advanced Prostate Cancer (AUA 2025) - "JG231, an innovative HSP70 inhibitor, enhances the therapeutic effectiveness of the AURKA inhibitor Alisertib in treating NEPC by modulating N-Myc protein stability and degradation."

Metastases • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • CHGA • MYCN

Dual Targeting of Aurora-A and Bcl-xL Synergistically Reshapes the Immune Microenvironment and Induces Apoptosis in Breast Cancer. (PubMed, Cancer Sci) - "Furthermore, the synergistic effect of MLN8237 and ABT263 in inducing intrinsic apoptosis was primarily driven by the inhibition of the AKT-Mcl-1 and Bcl-xL survival pathways in cultured tumor cells. Together, these findings support the MLN8237-ABT263 combination as an effective treatment strategy for TNBC, promoting both immune-mediated extrinsic apoptosis and inactivation of Bcl-xL/Mcl-1-dependent intrinsic anti-apoptotic pathways."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKA • BCL2L1 • CD8 • GZMB • IFNG

LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation (APASL 2025) - "Our study uncovers a negative functional loop of METTL16-TIALD-AURKA axis, and identifies a new mechanism for METTL16 mediated m6A-induced decay of TIALD on AURKA signaling in HCC progression, which may provide potential prognostic and therapeutic targets for HCC."

Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • AURKA • METTL16

Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies. (PubMed, Cell Death Discov) - "Replicative, mitotic, oxidative, and genotoxic forms of TIS were induced in p16-null/p53-proficient, BAX-deficient, and BRCA1-mutant cancer cells using mechanistically distinct TIS-inducing cancer therapeutics, including palbociclib, alisertib, doxorubicin, bleomycin, and olaparib...Furthermore, regardless of senescence-inducing therapeutic, stable/transient senescence acquisition, or genetic context, all TIS phenotypes shared a variable but significant senolytic response to the BCL-xL-selective BH3 mimetic A1331852. These findings may help to rethink the traditional assumption of the primed apoptotic landscape of TIS cancer cells. BCL-xL is a conserved anti-apoptotic effector of the TIS BCL2/BH3 interactome that can be exploited to maximize the efficacy of "one-two punch" senogenic-senolytic strategies."

BRCA Companion diagnostic • IO biomarker • IO Companion diagnostic • Journal • PARP Companion diagnostic • Oncology • BAX • BCL2 • BCL2L1 • BRCA1

Synthesis, Characterization, Bioevaluation, and Docking Studies of Spiroisatin-based Hydrazide Conjugates. (PubMed, Chem Biodivers) - "Specifically, the compounds IV-n and IV-p showed a high biosimilarity with the orally active iron chelator deferasirox, and IV-m showed high a biosimilarity with the kinase inhibitor alisertib...Pharmacokinetic studies revealed that the synthesized conjugates have good oral bioavailability, balanced hydrophilicity and minimal toxicity. The results of this study clearly highlight the potential of these conjugates as promising small bioactive molecules."

Journal • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • AURKA

Alisertib, Bortezomib, and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or B-cell Low Grade Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4

Alisertib Plus Endocrine Therapy Is Under Evaluation in HR+/HER2-Negative Metastatic Breast Cancer (OncLive) - "The ongoing phase 2 ALISCA-Breast1 study (NCT06369285) is evaluating the efficacy, safety, and optimal dose of alisertib (MLN8237) in combination with endocrine therapy in patients with hormone receptor (HR)–positive, HER2-negative recurrent or metastatic breast cancer previously treated with at least 2 lines of endocrine therapy....Recruitment is ongoing at an estimated 50 sites across the United States and Europe with a planned sample size of 150 patients. An interim analysis for safety and efficacy will be conducted after approximately 75 patients have completed at least 2 tumor assessments or experienced documented disease progression. The estimated study duration is approximately 56 months."

Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Puma Biotechnology Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "...'We anticipate the following key milestones over the next 12 months: (i) presentation of interim data from the Phase I trial of neratinib given in combination with trastuzumab deruxtecan in solid tumors with HER2 alterations (H1 2025); (ii) presentation of interim data from ALISCA-Breast1, a Phase II trial of alisertib in combination with endocrine treatment in patients with chemotherapy-naïve HER2-negative, hormone receptor-positive metastatic breast cancer (2025); and (iii) presentation of additional interim data from the ALI-4201/ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (2025)'."

P1 data • P2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Small Cell Lung Cancer

The AURKA inhibitor alters the immune microenvironment and enhances targeting B7-H3 immunotherapy in glioblastoma. (PubMed, JCI Insight) - "What's more, the combination of AURKA inhibitor (alisertib) and anti-B7-H3 antibody markedly reduced tumor size and promoted CD8+ T cell infiltration and activation in mouse orthotopic syngeneic glioma models. To our knowledge, this study is the first to demonstrate AURKA-mediated B7-H3 upregulation in glioma cells; moreover, it proposes a promising therapeutic strategy combining the AURKA inhibitor alisertib with B7-H3-specific blocking mAbs."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • CD8 • EGFR