alisertib (MLN8237) / Takeda, Puma - LARVOL DELTA

ALISCA-Lung2: A Study of Alisertib and Paclitaxel in Patients With Small Cell Lung Cancer (SCLC) (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Puma Biotechnology, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Inhibition of Aurora Kinase A Prevents Malignant Transformation in Oral Leukoplakia. (PubMed, J Oral Pathol Med) - "Increased AURKA expression may represent an early molecular event in OLK carcinogenesis, and targeting AURKA with alisertib is a candidate for potential applications in the management of OLK."

Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • AURKA

Results of a phase 1b study of osimertinib plus sapanisertib or alisertib for osimertinib-resistant, EGFR-mutant non–small cell lung cancer (NSCLC). (ASCO 2022) - P1 | "Osimertinib with alisertib or sapanisertib is well tolerated in osimertinib-resistant, EGFR mutant NSCLC. The sapanisertib combination, but not the alisertib combination, demonstrates antitumor activity suggesting that mTOR inhibition warrants further exploration in this population. Biomarker analysis is ongoing to identify the molecular determinants of response and resistance to sapasertib."

P1 data • Anemia • Dental Disorders • Diabetes • Hematological Disorders • Leukopenia • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Stomatitis • AURKA • EGFR

ALISertib plus endocrine therapy (ET) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2–) recurrent or metastatic breast CAncer (MBC): the randomized phase 2 ALISCA-Breast1 study (ESMO 2026) - No abstract available

Clinical • 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 + paclitaxel in patients with small cell lung cancer: The phase 2 ALISCA-Lung2 study (ESMO 2026) - No abstract available

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Puma Biotechnology Initiates ALISCA-Lung2, a Phase II Trial of Alisertib in Combination with Paclitaxel for the Treatment of Patients with Advanced Small Cell Lung Cancer (Businesswire) - "The ALISCA-Lung2 trial is a sequential dose escalation study that will enroll approximately 50 patients with small cell lung cancer who have progressed on or after treatment with platinum-based chemotherapy and immunotherapy. The primary endpoint of the trial is the safety and tolerability of alisertib when administered with paclitaxel. Secondary endpoints include objective response rate, duration of response, disease control rate, progression-free survival and overall survival."

Trial status • Small Cell Lung Cancer

Glypican-1 in Rhabdomyosarcoma: A Multi-omics Exploration of a Targetable Biomarker. (PubMed, Recent Pat Anticancer Drug Discov) - "GPC1 is aberrantly expressed in rhabdomyosarcoma, influencing neoplastic signaling and treatment responses, and new patents emphasize its potential for therapeutic targeting and diagnostic purposes GPC1 is aberrantly overexpressed, readily accessible to ligands or other molecules, and is a functionally significant biomarker in rhabdomyosarcoma, with emerging potential for diagnostic purposes and targeted therapy development."

Biomarker • Journal • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • GPC1

Safety Findings From the Phase 2 ALISCA-Lung1 Study of Alisertib in Patients With Small Cell Lung Cancer (SCLC) (IASLC-WCLC 2026) - P2 | "G-CSF prophylaxis has helped mitigate Grade 3/4 neutropenic events to levels lower than those observed historically (12% vs 42%), allowing an increase in alisertib dose to 60 mg BID. Updated data will be presented."

Clinical • IO biomarker • P2 data • CNS Disorders • Febrile Neutropenia • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor • Thrombocytopenia

Alisertib, an Aurora Kinase a Inhibitor, Induces Apoptosis and Autophagy but Inhibits Epithelial to Mesenchymal Transition in Human Epithelial Ovarian Cancer Cells [Retraction]. (PubMed, Drug Des Devel Ther) - "[This retracts the article DOI: 10.2147/DDDT.S74062.]."

Journal • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • AURKA

Nanoparticles-mediated dual drug administration boosts therapeutic efficacy in drug resistant melanoma. (PubMed, J Control Release) - "Furthermore, we developed a dual-drug delivery system co-loading trametinib, MEK inhibitor, and alisertib, Aurora A kinase inhibitor. This formulation was optimized to maintain a previously established synergistic ratio which effectively overcome acquired resistance to standard-of-care therapies and induce durable tumor regression. Collectively, these findings establish the PLGA-NPs platform as a robust, clinically relevant strategy to enhance the pharmacokinetic profile of treatments for metastatic and drug-resistant melanoma."

Journal • Melanoma • Oncology • Solid Tumor • Transplantation • AURKA

Thiadiazolo-Triazolo-Pyrimidine Hybrids as Dual Aurora A/ERK Inhibitors: Design, Synthesis, and Apoptotic Activity. (PubMed, Drug Dev Res) - "Among the synthesized hybrids, 9a, 9c, and 14b demonstrated higher cytotoxic action than alisertib and GDC-0994 against the MCF-7 and A549 cancer cell lines. They effectively induced pre-G1 phase, G0/G1 phase apoptosis, and G2/M phase arrest. The synthesized hybrids possessed favorable binding interactions in the molecular docking investigations as well as appropriate drug-like characteristics."

IO biomarker • Journal • Oncology • AURKA • BCL2 • CASP7 • CASP9 • FOXO3 • MAP2K1 • MYC

WSB1-Mediated PSMA Ubiquitination Promotes Enzalutamide-Induced Neuroendocrine-like Transition in Patient-Derived Prostate Cancer Spheroids. (PubMed, Int J Mol Sci) - "WSB1 depletion, AURKA inhibition with alisertib, and combined AURKA inhibition with EZH2 suppression reduced resistant aggregate growth and increased apoptosis-associated markers in patient-derived enzalutamide-resistant neuroendocrine-like spheroids and related models. These findings nominate the AURKA-WSB1-PSMA axis as a therapeutic vulnerability in refractory prostate cancer."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation • AR • KLK3 • SYP • WSB1

NCI-2019-05913: Alisertib in Combination With Osimertinib in Metastatic EGFR-mutant Lung Cancer (clinicaltrials.gov) - P1 | N=23 | Completed | Sponsor: Collin Blakely | Recruiting ➔ Completed | N=38 ➔ 23 | Trial completion date: Dec 2026 ➔ Oct 2025 | Trial primary completion date: Dec 2026 ➔ Oct 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • TP53

Discovery of Novel AURKA Inhibitors for Triple-Negative Breast Cancer (TNBC) Therapy via a Hybrid Virtual Screening Pipeline, Biological Evaluation and Molecular Dynamics Simulation. (PubMed, ACS Omega) - "Cell-based assays demonstrated that compound 3 produced stronger short-term cell-growth inhibition in MDA-MB-231 (TNBC) cells compared to clinical benchmarks MLN8237 and CCT241736, whereas compounds 3 and 5 showed cell-growth inhibition in NIH/3T3 cells within the same concentration range as the reference inhibitors...Additional computational analyses further provided supportive information for subsequent lead optimization. This study provides a transparent and open-source workflow for AI-assisted identification of AURKA-active chemotypes."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

…Key milestones over the next 12 months (Businesswire) - "(i) initiation of enrollment in ALISCA-Lung2, a Phase I/II trial of alisertib in combination with paclitaxel for the treatment of patients with extensive stage small cell lung cancer (Q3 2026); (ii) expansion of enrollment in 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 2026); (iii) expansion of ALISCA-Lung1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive stage small cell lung cancer (H2 2026); and (iv) presentation of updated 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 (Q4 2026)."

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

ALISCA-Breast1: A Study of Alisertib in Combination With Endocrine Therapy in Patients With HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=225 | Recruiting | Sponsor: Puma Biotechnology, Inc. | N=150 ➔ 225 | Trial completion date: Dec 2028 ➔ Jun 2029 | Trial primary completion date: Jun 2027 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2

Aurora kinase B as a therapeutic target in HPV-induced cervical cancer: mechanisms and future perspectives. (PubMed, Front Oncol) - "Although clinical evaluation of these AURKB inhibitors such as barasertib (AZD1152) and AZD2811 remains limited, early findings support their potential efficacy, particularly in rationally designed combination regimens. This review describes the mechanistic interplay between HPV oncogenes and AURKB, highlights its role as a biomarker of aggressive disease, and critically assesses the therapeutic promise of AURKB inhibition. Finally, we outline future perspectives on integrating AURKB-targeted therapies into precision oncology for HPV-driven cervical cancer."

Journal • Review • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor • AURKB

Targeting Aurora A Kinase to Overcome Treatment Resistance in Advanced HR+/HER2+ Breast Cancer (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: University of Wisconsin, Madison

Biomarker • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Small molecule drug screening, chemoinformatics and integrative transcriptomics identify targetable MYC-dependent therapeutic vulnerabilities in high-risk medulloblastoma (ISPNO 2026) - "Inhibition of AURKA (with alisertib) and CHEK1 (with prexasertib) was found to significantly extend survival and reduce tumour burden. Our findings demonstrate dual-AURKA/CHEK1 inhibition exerts a robust anti-tumour effect in MYC-MBG3 that warrants clinical evaluation. Importantly, we present an integrative screening pipeline which encompasses human tumour analysis and avatar-based screening to uncover actionable therapeutic vulnerabilities in MYC-MBG3, which is readily adaptable to other high-risk medulloblastoma disease features."

Brain Cancer • Medulloblastoma • Solid Tumor • MYC • PLK1

Predicting Early Tumor Progression in Patients with Atypical Teratoid/Rhabdoid Tumor with Longitudinal CSF Liquid Biopsies: A Report from Phase 2 Study (SJATRT) stratum B1. (ISPNO 2026) - "Treatment consisted of postoperative induction chemotherapy till >12 months of age, and then focal RT followed by consolidation chemotherapy and maintenance with alisertib... PFS and OS were not improved for patients enrolled in stratum B1 in SJATRT. Positive ctDNA in CSF, as a time-dependent covariate, was associated with worse PFS and OS in non-metastatic ATRT. Positive MRD at early time points may predict early relapse and serve as a biomarker for therapeutic intervention in future trials."

Biopsy • Clinical • Liquid biopsy • P2 data • Brain Cancer • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • SMARCA4 • SMARCB1

Alisertib Induces Cell Cycle Arrest and Autophagy and Suppresses Epithelial-to-Mesenchymal Transition Involving PI3K/Akt/mTOR and Sirtuin 1-Mediated signaling pathways in Human Pancreatic Cancer Cells [Retraction]. (PubMed, Drug Des Devel Ther) - "[This retracts the article DOI: 10.2147/DDDT.S75221.]."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

Fatty acid synthesis therapy-induced senescence (FASTIS) in cancer cells. (PubMed, Cell Death Dis) - "mRNA sequencing reveals an FASTIS-associated transcriptomic profile that overlaps between ACC and FASN inhibitors yet differs significantly from that of other mechanistically diverse TIS inducers, including bleomycin, alisertib, doxorubicin, and palbociclib. The FASTIS phenomenon is a therapeutic outcome through which cancer cells adapt to survive clinical-grade lipogenesis inhibitors. The cholesterol-addicted FASTIS fate can be rationally exploited as a collateral sensitivity in "one-two punch" senogenic-(immuno)senolytic strategies."

IO biomarker • Journal • Immunology • Oncology • BCL2L1 • IFNG • MIR146A • PD-L1

A first-in-human trial in advanced liver cancer guided by an in vivo CRISPR screen (EACR 2026) - P=N/A | "The combination of lenvatinib with AURKA inhibitors alisertib or vic-1911 exhibited robust antitumor effects across CDXs, PDOs, PDXs, immunocompetent mouse models, and 3D but not 2D culture. We identified AURKA as an in vivo-specific synthetic target of lenvatinib and combined AURKA inhibition with lenvatinib exhibited potent early clinical activity in HCC. This work provides proof-of-concept that in vivo CRISPR screen-guided target discovery can be successfully translated to early-phase clinical evaluation, establishing a promising combinatorial strategy for advanced HCC."

First-in-human • Metastases • P1 data • Preclinical • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • DDR1

NIR-II Imaging-Guided Phototherapy-Induced Senescence Reprograms Immunosuppressive Tumor Microenvironment for Potent Cancer Immunotherapy. (PubMed, ACS Nano) - "We developed a reactive oxygen species-responsive nanoplatform that co-delivers a second near-infrared emissive phototheranostic molecule with aggregation-induced emission characteristics and the Aurora kinase inhibitor alisertib...Importantly, it establishes durable immunological memory, preventing postoperative recurrence without systemic toxicity. By integrating phototherapy-enhanced drug delivery with SASP-driven immunosurveillance, our study introduces senescence induction as a promising paradigm for next-generation photoimmunotherapy."

Biomarker • IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Prospective prediction of alisertib-induced Aurora-A kinase resistance mutations in patients with metastatic ER+ breast cancer using an innovative artificial intelligence approach. (ASCO 2026) - "A structure-aware AI platform prospectively identified clinically relevant, treatment-induced AURKA resistance mutations prior to experimental detection. These findings demonstrate the feasibility of predictive modeling to anticipate resistance mechanisms and support the development of next-generation AURKA inhibitors optimized to overcome mutations-driven resistance and to improve therapeutic efficacy, safety and durability."

Clinical • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AURKA