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

Phase 2

Recruiting

• Conditions: Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Therapy
• Interventions: Drug: Palbociclib; Drug: Ribociclib; Drug: Abemaciclib; Drug: Letrozole

• Registration Number: NCT05766410
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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

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.

Study Timeline

• Status Verified: 2022-09
• Study Start: 2022-09-16
• Study First Submitted: 2023-02-03
• Study First Submitted QC: 2023-03-02
• Study First Posted: 2023-03-13
• Last Update Submitted: 2023-03-15
• Last Update Posted: 2023-03-16
• Primary Completion: 2025-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Palbociclib/Letrozole	Letrozole	CDK4, 6 inhibitor and endocrine therapy
Abemaciclib/Letrozole	Letrozole	CDK4, 6 inhibitor and endocrine therapy
Palbociclib/Letrozole	Palbociclib	CDK4, 6 inhibitor and endocrine therapy
Ribociclib/Letrozole	Ribociclib	CDK4, 6 inhibitor and endocrine therapy
Ribociclib/Letrozole	Letrozole	CDK4, 6 inhibitor and endocrine therapy
Abemaciclib/Letrozole	Abemaciclib	CDK4, 6 inhibitor and endocrine therapy

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adverse events	4 months	According to CTCAE 4.03

Trial Locations

Locations (2)

Department of Oncology, National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan

Department of Oncology,National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan