ABemaciclib, ET ± paclItaxel in aGgressive HR+/HER2- MBC trIaL

NCT04603183 | Completed Phase 2

• 2 other identifiers: MedOPP3212020-001648-24
• Study Type: interventional
• Target: 162
• Locations: 3 countries
• Sites: 31

Brief Summary

This is a multicenter, randomized, 2 arm, open label, phase II study. It is designed to compare the efficacy and safety of abemaciclib combined with ET (letrozole or fulvestrant) versus a short course with induction chemotherapy with paclitaxel followed by maintenance therapy with abemaciclib combined with ET (letrozole or fulvestrant) in patients with previously untreated, unresectable locally advanced, or metastatic HR positive/HER2 negative breast cancer with aggressive disease criteria.

Conditions

Breast Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• 12-week overall response rate (ORR)

  Complete response (CR) or partial response (PR), during the first 12 weeks of treatment as per blinded independent central review, using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

  12 weeks

Secondary Outcomes (13)

• ORR

  Baseline up to 24 months

• Clinical benefit rate (CBR)

  Baseline up to 24 months

• 12-week progression-free survival (PFS) rate

  Baseline up to 12 weeks

• PFS

  Baseline up to 24 months

• Time to response (TTR)

  Baseline up to 24 months

Study Arms (2)

Interventional Arm (Arm A)

EXPERIMENTAL

Abemaciclib 150 mg orally twice daily (BID) during each 28 day cycle combined with ET (2.5 mg letrozole, orally administered and taken daily during each 28-day cycle, or 500 mg fulvestrant, by intramuscular \[IM\] administration on Days 1 and 15 (±3 days) of the first treatment cycle and Day 1 of each cycle thereafter.

Drug: Abemaciclib; Drug: Letrozole; Drug: Fulvestrant

Control Arm (Arm B)

ACTIVE COMPARATOR

Paclitaxel 90 mg/m² infused over 1 hour on Days 1, 8, and 15 of the 28 day cycle, with at least a 6-day time span between separated doses.

Drug: Paclitaxel

Interventions

Abemaciclib DRUG

Patients will receive abemaciclib 150 mg orally twice daily (BID) (300 mg daily, administered as six 50 mg tablets) during each 28 day cycle combined with either letrozole or fulvestrant.

Also known as: Verzenios

Interventional Arm (Arm A)

Paclitaxel DRUG

Paclitaxel 90 mg/m² infused over 1 hour on Days 1, 8, and 15 of the 28 day cycle, with at least a 6-day time span between separated doses.

Also known as: Paclitaxel Teva

Control Arm (Arm B)

Letrozole DRUG

Patients will receive 2.5 mg letrozole, orally administered and taken daily during each 28-day cycle combined with abemaciclib.

Interventional Arm (Arm A)

Fulvestrant DRUG

Patients will receive 500 mg fulvestrant, by intramuscular \[IM\] administration on Days 1 and 15 (±3 days) of the first treatment cycle and Day 1 of each cycle thereafter combined with abemaciclib.

Interventional Arm (Arm A)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form (ICF) prior to participation in any study-related activities.
• Male or female patients ≥18 years at the time of signing the ICF.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Life expectancy of at least 24 weeks.
• Pre-menopausal, peri-menopausal, and post-menopausal women as defined by any of the following criteria:
• Documented bilateral oophorectomy;
• Age ≥60 years;
• Age \<60 years and cessation of regular menses for ≥12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and/or FSH level within the laboratory's reference range for post-menopausal females.
• Unresectable locally advanced or metastatic breast cancer (MBC) that is not amenable to resection with curative intent.
• At least one of the following aggressive disease criteria:
• Presence of visceral disease;
• Either radiological as per RECIST v1.1 or clinical evidence of progressive disease (PD) on or within 36 months of completing adjuvant endocrine therapy (ET);
• High histological grade and/or PgR-negative status on primary tumor;
• LDH \>1.5 × the upper limit of normal (ULN).
• Histologically confirmed estrogen receptor-positive and/or progesterone receptor (PgR)-positive (with ≥1% positive stained cells according to National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines) and HER2-negative (0 to 1+ by immunohistochemistry or 2+ and negative by in situ hybridization test) breast cancer based on local testing on the most recent analyzed biopsy.

You may not qualify if:

• Known hypersensitivity to abemaciclib, letrozole, fulvestrant, paclitaxel, and/or any of their excipients.
• Are currently receiving an investigational drug in a clinical study or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Note: For patients who stopped receiving an investigational drug in another clinical study, a washout period of 21 days or 5-half-lives (whichever is shorter) must be observed before entering the trial.
• Formal contraindication to ET defined as visceral crisis and rapidly or symptomatic progressive visceral disease.
• Known concurrent malignancy or malignancy within 5 years of study enrollment except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the medical monitor is required.
• Known active brain metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for ≥4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for ≥14 days prior to first dose of study treatment.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Major surgical procedure within 14 days prior to treatment initiation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis.
• Note: Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.
• Active bleeding diathesis venous thrombo-embolism, previous history of bleeding diathesis, or chronic anti-coagulation treatment, or any indications or history of Disseminated Intravascular Coagulation (DIC) or Deep vein thrombosis (DVT).
• Serious and/or uncontrolled pre-existing 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 \[e.g., estimated creatinine clearance \<30 ml/min\], history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn's disease or ulcerative colitis or a pre-existing chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Active bacterial or fungal infection at the time of enrolment (requiring antibiotics or antifungal agents at time of initiating study treatment).
• 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.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through a period of 3 weeks to 2 years after the last dose of study treatment.

Sponsors & Collaborators

• MedSIR: lead
• Eli Lilly and Company: collaborator

Study Sites (31)

Instituto Europeo di Oncologia

Milan, 20141, Italy

Location

Ospedale San Gerardo

Monza, 20900, Italy

Location

Ospedale Guglielmo da Saliceto

Piacenza, 29121, Italy

Location

Azienda Ospedaliero-Universitaria Cittá de la Salute e della Scienza

Torino, 10126, Italy

Location

Hospital Fernando da Fonseca

Amadora, 2720-276, Portugal

Location

Hospital de Santa Maria - Centro Hospitalar Lisboa Norte

Lisbon, 1600-190, Portugal

Location

Hospital Universitario Virgen del Rocio

Seville, Andalusia, Spain

Location

Fundación Althaia Manresa

Manresa, Barcelona, 08243, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Centro Oncoloxico de Galicia

A Coruña, Coruña, 15009, Spain

Location

Complejo Asistencial Universitario De León

León, Leon, 24073, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Pamplona/Iruña, 31008, Spain

Location

Hospital Universitari de Sant Joan de Reus

Reus, Tarragona, 43204, Spain

Location

Hospital General Universitario de Alicante

Alicante, 03010, Spain

Location

Hospital Quiron Salud Dexeus

Barcelona, Spain

Location

Hospital Universitario Basurto

Bilbao, 48013, Spain

Location

Consorcio Hospitalario Provincial de Castellon

Castellon, 12002, Spain

Location

Institut Catala D'Oncologia Girona - Hospital Josep Trueta

Girona, 17007, Spain

Location

Hospital Universitario San Cecilio

Granada, 18016, Spain

Location

Hospital Universitario Arnau de Vilanova

Lleida, 25198, Spain

Location

Hospital Ruber Juan Bravo

Madrid, 28006, Spain

Location

Hospital Beata María Ana

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Quirónsalud Sagrado Corazón

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Quironsalud Valencia

Valencia, 460137, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital Arnau de Vilanova

Valencia, 46015, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

MeSH Terms

Interventions

abemaciclib; Paclitaxel; Letrozole; Fulvestrant

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Antonio Llombart-Cussac

  Arnau de Vilanova Hospital, Valencia (Spain)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 26, 2020
• Study Start: June 2, 2021
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2025
• Last Updated: December 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (25); PT (2); IT (4)