TPS 105 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

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement42nd Annual Miami Breast Cancer Conference® - Abstracts
Volume 39
Issue 4
Pages: 43-44

TPS 105 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

TPS 105 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

Background

Despite the wide range of available treatment options for patients with hormone receptor–positive/HER2-negative (HR+/HER2–) recurrent or metastatic breast cancer, optimal treatment after progression on CDK4/6 inhibitors (CDK4/6i) remains unclear. Several mechanisms of resistance to CDK4/6i have been postulated, including increased expression of Aurora kinase A (AURKA), a key regulator of mitosis associated with poor prognosis in multiple tumor types. Further implicated in CDK 4/6i resistance, high c-Myc or RB1 loss of function (LOF) have been associated with transcriptional co-regulation or synthetic lethality, respectively, with AURKA. Alisertib is a highly selective, reversible, ATP-competitive, orally administered, small-molecule AURKA inhibitor with antiproliferative activity in HR+ breast cancer-derived cell lines and breast cancer xenograft models. Greater alisertib sensitivity has been reported in models with elevated AURKA or c-Myc expression, or RB1 LOF. Clinically, alisertib showed efficacy in phase 1 and 2 trials, including objective response rates (ORRs) of 19.6% to 20% and median progression-free survival (PFS) of 5.4 months to 5.6 months alone or with fulvestrant in patients with HR+/HER2–, endocrine-resistant MBC. The most common treatment-related grade ≥ 3 adverse events (AEs) were neutropenia, anemia, and leukopenia.

Methods

ALISCA-Breast1 (NCT06369285) is a randomized phase 2 study. Primary objective: to determine the optimal alisertib dose level administered with selected endocrine therapy (ET) for use in future studies based on observed safety (AEs, serious AEs per CTCAE v5.0) and efficacy (ORR, duration of response, disease-control rate, PFS, overall survival). Secondary objectives: to identify biomarkers correlating with efficacy; to evaluate alisertib pharmacokinetics (PK). Key inclusion criteria: age 18 years or older; ECOG performance status 0 or 1; confirmed HR+, HER2–, recurrent or metastatic breast adenocarcinoma not amenable to curative therapy; available tumor tissue for biomarker analyses; progression on or after 2 or more prior ET lines in recurrent or metastatic setting; prior CDK4/6i with ET in recurrent or metastatic setting; 1 or more measurable target lesion per RECIST v1.1. Patients who are premenopausal are eligible if amenable to treatment with a luteinizing hormone-releasing hormone agonist. Key exclusion criteria: prior chemotherapy in recurrent or metastatic setting; bone-only disease not meeting the measurability definition per RECIST v1.1; prior AURKA-specific or pan-Aurora-targeted agents; active infection; patients who are immunocompromised; unstable brain metastases; uncontrolled symptomatic visceral disease. 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. Up to 50 patients will be enrolled per arm at multiple centers in the US and Europe. Treatment will continue until disease progression, unacceptable toxicity, or consent withdrawal. Stratification factors: time to recurrence/progression after initiating CDK4/6i therapy (< 12 months or ≥ 12 months); presence of visceral disease (yes/no). All patients will undergo sparse PK sampling. 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.

Articles in this issue

40 Frequency of Documented IHC Score in Patients With HER2-Negative Breast Cancer in the US: An Observational Study Using Guardian Research Network Data
40 Frequency of Documented IHC Score in Patients With HER2-Negative Breast Cancer in the US: An Observational Study Using Guardian Research Network Data
41 Provider Preferences and Practices in Testing and Reporting HER2 Immunohistochemistry in Patients With Breast Cancer: A Survey and Interview Study Among US Pathologists and Oncologists
41 Provider Preferences and Practices in Testing and Reporting HER2 Immunohistochemistry in Patients With Breast Cancer: A Survey and Interview Study Among US Pathologists and Oncologists
42 Exploring the Treatment Gap in High-Risk HR+, HER2– Early Breast Cancer: Eligible Patients Not Receiving Abemaciclib in the US
42 Exploring the Treatment Gap in High-Risk HR+, HER2– Early Breast Cancer: Eligible Patients Not Receiving Abemaciclib in the US
TPS 43 ADELA: A Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus vs Elacestrant + Placebo in ER+/HER2– Advanced Breast Cancer Patients With ESR1-Mutated Tumors Progressing on Endocrine Therapy
TPS 43 ADELA: A Double-Blind, Placebo-Controlled, Randomized Phase 3 Trial of Elacestrant + Everolimus vs Elacestrant + Placebo in ER+/HER2– Advanced Breast Cancer Patients With ESR1-Mutated Tumors Progressing on Endocrine Therapy
45 A Phase 3 Randomized Study of Adjuvant Sacituzumab Tirumotecan Plus Pembrolizumab vs Treatment of Physician’s Choice in Patients With Triple-Negative Breast Cancer Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response at Surgery
45 A Phase 3 Randomized Study of Adjuvant Sacituzumab Tirumotecan Plus Pembrolizumab vs Treatment of Physician’s Choice in Patients With Triple-Negative Breast Cancer Who Received Neoadjuvant Therapy and Did Not Achieve a Pathological Complete Response at Surgery
46 Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy Followed by Adjuvant Pembrolizumab or Placebo for High-Risk, Early-Stage Triple-Negative Breast Cancer: Overall Survival and Subgroup Results From the Phase 3 KEYNOTE-522 Study
46 Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy Followed by Adjuvant Pembrolizumab or Placebo for High-Risk, Early-Stage Triple-Negative Breast Cancer: Overall Survival and Subgroup Results From the Phase 3 KEYNOTE-522 Study
48 Prevalence of “HER2 Ultra-Low” Among Advanced Breast Cancer Patients With Historical IHC0 Status
48 Prevalence of “HER2 Ultra-Low” Among Advanced Breast Cancer Patients With Historical IHC0 Status
49 Clinical Characteristics and Treatment Persistence in US Patients With HR+/HER2–, Node-Positive Early Breast Cancer Treated With Abemaciclib: Real-World Study From First Year After Approval
49 Clinical Characteristics and Treatment Persistence in US Patients With HR+/HER2–, Node-Positive Early Breast Cancer Treated With Abemaciclib: Real-World Study From First Year After Approval
52 Correlation and Prediction of Complete Pathologic Response Rates and Ki-67 in Patients Receiving Neoadjuvant Immunotherapy for Triple-Negative Breast Cancer
52 Correlation and Prediction of Complete Pathologic Response Rates and Ki-67 in Patients Receiving Neoadjuvant Immunotherapy for Triple-Negative Breast Cancer
53 Comparison of Surgical Complications With Direct-to-Implant vs Tissue Expander Reconstruction After Wise Pattern Skin-Sparing Mastectomy
53 Comparison of Surgical Complications With Direct-to-Implant vs Tissue Expander Reconstruction After Wise Pattern Skin-Sparing Mastectomy
54 The Treatment of Breast Cancer With Percutaneous Thermal Ablation: Results of the THERMAC Trial
54 The Treatment of Breast Cancer With Percutaneous Thermal Ablation: Results of the THERMAC Trial
55 Do Genetic Counseling and Testing Affect Rates of Contralateral Prophylactic Mastectomy in Patients Without Clinically Actionable Mutations?
55 Do Genetic Counseling and Testing Affect Rates of Contralateral Prophylactic Mastectomy in Patients Without Clinically Actionable Mutations?
56 Paternal vs Maternal Inheritance of a BRCA Mutation: Is There a Difference in Presentation and Stage of Breast Cancer at Diagnosis?
56 Paternal vs Maternal Inheritance of a BRCA Mutation: Is There a Difference in Presentation and Stage of Breast Cancer at Diagnosis?
57 Tumor Morphology Concordance in Multifocal/Multicentric Triple- Negative and HER2+ Breast Cancers
57 Tumor Morphology Concordance in Multifocal/Multicentric Triple- Negative and HER2+ Breast Cancers
59 Are Choosing Wisely Guidelines Applicable to Patients With a High Ki-67 Proliferation Index and Magee Equation Score?
59 Are Choosing Wisely Guidelines Applicable to Patients With a High Ki-67 Proliferation Index and Magee Equation Score?
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