Phase 3  

MONARCH 2; NCT02107703

Breast Cancer

CDK4 & 6 Inhibitor


A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Fulvestrant With or Without Abemaciclib, a CDK4 & 6 Inhibitor, for Women With Hormone-Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer*

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Key Inclusion Criteria
  • Hormone-receptor-positive (HR+), HER2-negative breast cancer
  • Locally advanced disease not amenable to curative treatment by surgery or metastatic disease, and must meet one of the following criteria:
    • Relapsed with radiologic evidence of progression while receiving neoadjuvant/adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression
    • Relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression
    • Relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than one line of endocrine therapy or any prior chemotherapy for metastatic disease
    • Presented de novo with metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than one line of endocrine therapy or any prior chemotherapy for metastatic disease
    • For the endocrine-naïve cohort, must not have received prior endocrine therapy in current or prior disease setting
  • Postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to day 1 of cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
  • Negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if postmenopausal status is due to ovarian suppression with a GnRH agonist
  • Measurable disease or nonmeasurable bone-only disease
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Discontinued previous therapies for cancer (including aromatase inhibitors, antiestrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least grade 1) except for residual alopecia or peripheral neuropathy
Key Exclusion Criteria
  • 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
  • Visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis
  • Clinical evidence or history of central nervous system metastasis
  • Prior treatment with chemotherapy (except for neoadjuvant/adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4 & 6 inhibitor. For the endocrine-naïve cohort: Treatment with any prior endocrine therapy
  • Yellow fever vaccination within 28 days prior to randomization
  • Major surgery within 14 days prior to randomization of study drug to allow for postoperative healing of the surgical wound and site(s)
  • Syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest within the last 12 months
  • Inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in situ of the cervix) unless in complete remission with no therapy for a minimum of 3 years
  • Received an autologous or allogeneic stem-cell transplant
  • Active bacterial, fungal, or viral infection
  • Initiation of bisphosphonates or approved receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents <7 days prior to randomization
*
This clinical trial is being conducted globally.
Abemaciclib 150 mg or placebo equivalent is administered PO Q12H.
Fulvestrant 500 mg is administered intramuscularly on days 1 and 15 of a 28-day cycle for cycle 1, then on day 1 for all subsequent cycles.
Contact the Lilly Oncology Clinical Trial Navigation Service

Visit www.clinicaltrials.gov for more information on this trial.

The safety and efficacy of the agents under investigation have not been established. There is no guarantee that the agents will receive regulatory approval and become commercially available for the uses being investigated.