A Randomized Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in ER+/HER2- EBC

Study Overview
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Brief Summary
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The 3 FDA-approved CDK4, 6 inhibitors, palbociclib, ribociclib, and abemciclib, all provided progression-free survival benefits when combined with endocrine therapy in advanced ER+/HER2- breast cancer. But, not all of them provided overall survival benefit in the same setting. One of the proposed mechanisms that influence the overall survival difference is from the different influence of the 3 CDK4, 6 inhibitors on tumor microenvironment and/ or immune system. However, there was no head-to-head comparison of the 3 CDK4, 6 inhibitors in the same study. Neoadjuvant therapy provides a window to obtain tissue samples before treatment, during treatment, and after treatment. We aim to compare the immune modulation effects of palbociclib, ribociclib, and abemaciclib with letrozole in neoadjuvant treatment for ER+/HER2- early breast cancer.

Detailed Description
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The 3 FDA-approved CDK4, 6 inhibitors, palbociclib, ribociclib, and abemciclib, all provided progression-free survival benefits when combined with endocrine therapy in advanced ER+/HER2- breast cancer. But, not all of them provided overall survival benefit in the same setting. One of the proposed mechanisms that influence the overall survival difference is from the different influence of the 3 CDK4, 6 inhibitors on tumor microenvironment and/ or immune system. However, there was no head-to-head comparison of the 3 CDK4, 6 inhibitors in the same study. Neoadjuvant therapy provides a window to obtain tissue samples before treatment, during treatment, and after treatment. We aim to compare the immune modulation effects of palbociclib, ribociclib, and abemaciclib with letrozole in neoadjuvant treatment for ER+/HER2- early breast cancer. We will collect tumor tissue, blood, and stool samples prospectively before treatment, at 2 weeks after treatment, and after 12 weeks of treatment at the time of surgery. Immune modulation effects will be compared between 3 treatment groups from breast tumor RNAseq analysis.

Official Title
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A Randomized, Open-label, Parallel-group Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in Early ER+/HER2- Breast Cancer

Conditions
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Breast Cancer, Hormone Receptor-positive Breast Cancer, Hormone Therapy

Intervention / Treatment
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* Drug: Palbociclib
* Drug: Ribociclib
* Drug: Abemaciclib
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged ≥ 20 years old at the time of informed consent. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory. with estrogen receptor positive (>10%) on IHC staining and HER2 negative (IHC 0+/1+, or IHC 2+ plus FISH negative) Stage II to III With adequate organ function ECOG 0-1 Exclusion Criteria: Pregnant or nursing (lactating) women Women of child-bearing potential unless using highly effective methods of contraception during study drug dosing and for 12 months post-dosing Patients with active systemic infections or known to have AIDS or to test positive for HIV antibody at Screening Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Palbociclib/Letrozole<br>CDK4, 6 inhibitor and endocrine therapy | Drug: Palbociclib<br>* CDK4, 6 inhibitor<br>* Other names: Ibrance;Drug: Letrozole<br>* Endocrine therapy<br>* Other names: Femara;|
| Active Comparator: Ribociclib/Letrozole<br>CDK4, 6 inhibitor and endocrine therapy | Drug: Ribociclib<br>* CDK4, 6 inhibitor<br>* Other names: Kisqali;Drug: Letrozole<br>* Endocrine therapy<br>* Other names: Femara;|
| Active Comparator: Abemaciclib/Letrozole<br>CDK4, 6 inhibitor and endocrine therapy | Drug: Abemaciclib<br>* CDK4, 6 inhibitor<br>* Other names: Venizio;Drug: Letrozole<br>* Endocrine therapy<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq | Characterization of RNAseq from serial tumor biopsy samples | Through study completion, an average of 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | According to CTCAE 4.03 | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDK4, 6 inhibitor, Neoadjuvant therapy, Hormone therapy, Hormone Receptor-positive Breast Cancer