Impact of Endocrine Therapy and Abemaciclib on Host and Tumor Immune Cell Repertoire/Function in Advanced ER+/HER2- Breast Cancer

NCT04352777 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: Pro00103625
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to perform an in depth analysis of changes in the tumor immune microenvironment in patients undergoing treatment with standard of care endocrine therapy and abemaciclib in the advanced setting via singe cell RNA sequencing. The investigators will also correlate changes in serum estrogen levels to changes in tumor and peripheral immune cell repertoire and function (including regulatory T cell populations, B cells, myeloid-derived suppressor cell populations, T cell activation and T cell exhaustion).This study has two cohorts with 15 patients in each cohort.

Conditions

Metastatic Breast Cancer; Locally Advanced Breast Cancer; Hormone Receptor Positive Tumor

Keywords

metastatic breast cancer; abemaciclib; endocrine therapy

Outcome Measures

Primary Outcomes (2)

• Changes in serum estrogen (E1 and E2) levels compared to changes in tumor immune cell repertoire and function in response to endocrine therapy and CDK 4/6 inhibition

  Estrogen levels in the blood will be assessed to correlate with changes in immune cell populations within the tumor.

  Through study completion, approximately 2 years

• Changes in serum estrogen (E1 and E2) levels compared to peripheral blood mononuclear cell repertoire and function in response to endocrine therapy and CDK 4/6 inhibition

  Estrogen levels in the blood will be assessed to correlate with changes in the characterization and functionality of peripheral blood mononuclear cells including regulatory T cell populations, B cells, myeloid-derived suppressor cell populations, T cell activation and T cell exhaustion.

  Through study completion, approximately 2 years

Secondary Outcomes (6)

• Changes in tumor immune cell populations in response to fulvestrant and aromatase inhibitor therapy plus abemaciclib, measured by sequential biopsies

  Baseline, 4 weeks

• Differences in tumor immune cell infiltrate and peripheral blood mononuclear cells in response to fulvestrant versus aromatase inhibition plus CDK4/6 inhibition, measured by sequential biopsies and blood collection

  Baseline, 4 weeks

• To correlate unique immune cell populations identified with progression free survival in the overall population

  Through study completion, approximately 2 years

• Best overall response rate of abemaciclib and endocrine therapy in both treatment arms

  Through study completion, approximately 2 years

• Progression free survival in response to abemaciclib and endocrine therapy in both treatment arms

  Through study completion, approximately 2 years

Study Arms (2)

Cohort 1

ACTIVE COMPARATOR

Fulvestrant plus abemaciclib

Drug: Abemaciclib; Drug: Fulvestrant

Cohort 2

ACTIVE COMPARATOR

Aromatase inhibitor plus abemaciclib (with or without ovarian suppression)

Drug: Abemaciclib; Drug: Aromatase Inhibitors

Interventions

Abemaciclib DRUG

50 - 150mg tablet BID as prescribed per standard of care

Cohort 1; Cohort 2

Fulvestrant DRUG

500mg as prescribed per standard of care

Cohort 1

Aromatase Inhibitors DRUG

Letrozole, anastrozole as prescribed per standard of care

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women age ≥ 18
• Locally advanced/unresectable or metastatic breast cancer
• Histologically documented estrogen receptor positive adenocarcinoma of the breast that is (any progesterone status allowed):
• ER positive defined as ≥ 10 % tumor cells positive for ER by immunohistochemistry (IHC), irrespective of staining intensity.
• HER2 negative status is determined by:
• IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within \> 10% of invasive tumor cells, or
• IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells, or
• FISH negative based on:
• Single-probe average HER2 copy number \< 4.0 signals / cell, or
• Dual-probe HER2/CEP17 ratio \< 2.0 with an average HER2 copy number \< 4.0 signals /cell
• Patients should have plans to initiate standard of care endocrine therapy with non-steroidal aromatase inhibitor (letrozole, anastrazole) OR fulvestrant plus abemaciclib in the advanced/metastatic first-line or second-line setting per treating oncologist discretion
• Patients should be willing and able to undergo fresh biopsy pretreatment and at 4 weeks into treatment.
• Patients should have an accessible lesion representative of recurrent or metastatic breast cancer for biopsy. Patients will undergo a tissue biopsy or tissue collection for research purposes only. Sites for tissue acquisition include the breast, skin/chest wall, soft tissue, liver, bone. Research directed lung biopsies and brain biopsies are not permitted. Procedures for tissue acquisition are restricted to those performed under local anesthesia or IV conscious sedation; biopsies that require general anesthesia are not permitted in this situation.
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization. A washout period of at least 21 days is required between last chemotherapy dose and randomization (provided the patient did not receive radiotherapy).
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy.

You may not qualify if:

• History of concurrent active malignancy within last 5 years (excluding basal cell skin cancer, resected squamous cell carcinoma of the skin)
• Current use of hormonal birth control (copper IUD allowed) or estrogen replacement therapy
• Active autoimmune disease that has required systemic treatment in past 6 months (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or similar treatment) is not considered a form of systemic treatment.
• History of a serious or life-threatening allergic reaction to local anesthetics (e.g., lidocaine, xylocaine) used during a biopsy procedure
• Immunodeficient subjects, E.G., receiving systemic steroid therapy greater than physiologic doses or any other form of immunosuppressive therapy within 30 days prior to the first dose of endocrine therapy treatment
• Concurrent use of other oncologic therapies in the adjuvant setting other than bisphosphonates
• Patients with disease not amenable to biopsy
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Females who are pregnant or lactating.
• The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• History of bleeding disorder that would make serial biopsies unsafe.
• Patients of active anticoagulation for history of venous thromboembolism, cardiovascular conditions.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

abemaciclib; Fulvestrant; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Sarah Sammons, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 20, 2020
• Study Start: September 14, 2020
• Primary Completion: June 25, 2025
• Study Completion: June 25, 2025
• Last Updated: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)