A Study of Nonsteroidal Aromatase Inhibitors Plus LY2835219 or Placebo in Postmenopausal Women With Breast Cancer

• Register: EUCTR
• Last refreshed on: 8 January 2024
• Main ID: EUCTR2014-001502-18-AT
• Date of registration: 17/10/2014
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Study of Nonsteroidal Aromatase Inhibitors Plus LY2835219 or Placebo in Postmenopausal Women With Breast Cancer
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Nonsteroidal Aromatase Inhibitors (Anastrozole or Letrozole) Plus LY2835219, a CDK4/6 Inhibitor, or Placebo in Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer With No Prior Systemic Therapy in This Disease Setting - Monarch 3
• Date of first enrolment: 24/11/2014
• Target sample size: 450
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001502-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: All patients will receive NSAI (anastrozole or letrozole) Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Canada, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Türkiye, United Kingdom, United States

Contacts

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

• Name: Clinical Trial Registry Office
• Affiliation: Eli Lilly

Key inclusion & exclusion criteria

Inclusion criteria:
• have a diagnosis of HR+, HER2- breast cancer;
• have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease;
• have postmenopausal status due to either surgical/natural menopause or amenorrheic (non-treatment-induced) for at least 12 months;
• have either measurable disease or nonmeasurable bone-only disease;
• have a performance status =1 on the Eastern Cooperative Oncology Group (ECOG) scale;
• have adequate organ function;
• have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture prior to randomization and recovered from the acute effects of therapy;
• are female and =18 years of age;
• are able to swallow tablets;

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 200

Exclusion criteria:
• have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis. Visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
• have inflammatory breast cancer.
• have clinical evidence or a history of CNS metastasis. Screening is not required for enrollment.
• are currently receiving or have previously received endocrine therapy for locoregionally recurrent or metastatic breast cancer. [Note: A patient may be enrolled if she received prior (neo)adjuvant endocrine therapy (including , but not limited to anti-estrogens or aromatase inhibitors) for localized disease. In addition, a patient may be enrolled if she has received =2 weeks of NSAI in this disease setting immediately preceding screening and agrees to discontinue NSAI until study treatment initiation.]
• have received prior (neo)adjuvant endocrine therapy (e.g., anti-estrogens or aromatase inhibitors) with a disease-free interval =12 months from completion of treatment.
• are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer. [Note: Patients may be enrolled if they received prior (neo)adjuvant chemotherapy for localized disease.]
• have received prior treatment with everolimus
• have received prior treatment with any CDK4/6 inhibitor (or participated in any CDK4/6 inhibitor clinical trial for which treatment assignment is still blinded)
• have initiated bisphosphonates or approved RANK ligand (RANK-L) targeted agents (for example, denosumab) <7 days prior to randomization
• are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study. If a patient is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and Lilly clinical research physician (CRP) is required to establish eligibility.
• have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively.
• have had major surgery within 14 days prior to randomization to allow for post-operative healing of the surgical wound and site(s).
• have received recent (within 28 days prior to randomization) yellow fever vaccination.
• have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis).
• have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Hormone Receptor Positive, HER2 negative Locoregionally Recurrent or Metastatic Breast Cancer with No Prior Systemic Therapy in This Disease Setting
MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Verzenios
Product Name: Abemaciclib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: abemaciclib
Other descriptive name: ABEMACICLIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Letrozole
Pharmaceutical Form: Film-coated tablet

Product Name: Anastrozole
Pharmaceutical Form: Film-coated tablet

Primary Outcome(s)

Main Objective: The primary objective of Study I3Y-MC-JPBM is to compare treatment with LY2835219 plus NSAI therapy versus placebo plus NSAI therapy with respect to PFS in postmenopausal women with HR+, HER2- locoregionally recurrent or metastatic breast cancer who have not received prior systemic therapy in this disease setting.

Primary end point(s): Progression Free Survival (PFS)

Secondary Objective: The secondary objectives of the study are to compare the combination treatment of LY2835219 and NSAI therapy versus placebo plus NSAI therapy with respect to the following:
• OS
• OS rate at 1, 2, and 3 years;
• ORR (CR + PR);
• Duration of response (CR + PR);
• DCR (CR + PR + SD);
• CBR (CR + PR + SD =6 months);
• Safety and tolerability;
• Change in symptom burden from baseline using the EORTC QLQ-C30, EORTC QLQ-BR23 (breast) questionnaire, and health status scores from the EQ-5D 5L;
• PK of LY2835219, its metabolites, and NSAI therapy

Timepoint(s) of evaluation of this end point: Baseline up to Measured Progressive Disease or Death from Any Cause (Approximately 34 Months)

Secondary Outcome(s)

Secondary end point(s): • Overall Survival (OS)
• Objective Response Rate (ORR)
• Duration of Response (DoR)
• Disease Control Rate (DCR):
• Clinical Benefit Rate (CBR)
• Safety and tolerability endpoints (e.g. physical examination, adverse event collection, lab tests, dosing information)
• Change in symptom burden using EORTC QLQ-C30, EORTC QLQ-BR23 questionnaire
• Change in health status using the EQ-5D 5L
• Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of LY2835219, its Metabolites, and NSAI Therapy:

Timepoint(s) of evaluation of this end point: OS: Baseline to approximately 82 Months

ORR, DoR, CBR, safety and tolerability endpoints (e.g. physical examination, adverse event collection, lab tests, dosing information change in symptom burden using the EORTC QLQ-C30, EORTC QLQ-BR23, change in health status using the EQ-5D 5L: Baseline to approximately 34 mont

PK: Baseline up to approximately 4 months

Secondary ID(s)

I3Y-MC-JPBM

2014-001502-18-SE

Source(s) of Monetary Support

Eli Lilly and Company

Ethics review

Status: Approved
Approval date: 06/11/2014
Contact: