Overview

A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer

Status:
Active, not recruiting
Trial end date:
2023-02-28
Target enrollment:
0
Participant gender:
Female
Summary
The main purpose of this study is to evaluate the efficacy of the study drug abemaciclib in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locoregionally recurrent or metastatic breast cancer.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Eli Lilly and Company
Treatments:
Anastrozole
Estradiol
Fulvestrant
Letrozole
Criteria
Inclusion Criteria:

- Have a diagnosis of HR+, HER2- breast cancer. Although not required as a protocol
procedure, metastatic disease should be considered for biopsy whenever possible to
reassess hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)
status if clinically indicated.

- To fulfill the requirement for HR+ disease, a breast cancer must express, by
immunohistochemistry (IHC), at least 1 of the HRs (estrogen receptor [ER],
progesterone receptor [PgR]) as defined in the relevant American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.

- To fulfill the requirement of HER2- disease, a breast cancer must not
demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of
HER2 by either IHC or in-situ hybridization as defined in the relevant ASCO/CAP
guidelines.

- Meet either Inclusion Criterion (2a) or Inclusion Criterion (2b). Participants meeting
Inclusion Criterion 2a will be enrolled in Cohort A and participants meeting Inclusion
Criterion 2b will be enrolled in Cohort B.

- (2a) Have locoregionally recurrent disease not amenable to resection or radiation
therapy with curative intent or metastatic disease.

- Relapsed with radiologic evidence of progression more than 1 year from completion
of adjuvant endocrine therapy and have received no prior endocrine therapy for
locoregionally recurrent or metastatic disease (Note: prior adjuvant endocrine
therapy for localized disease may have included, but is not limited to,
anti-estrogens or aromatase inhibitors. In addition, a participant 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.) OR

- Presented with de novo metastatic breast cancer (mBC) and not received any prior
endocrine therapy. OR

- Relapsed with radiologic evidence of progression less than 1 year from completion of
or while receiving adjuvant endocrine therapy (except for letrozole or anastrozole)
and have received no prior endocrine therapy for locoregionally recurrent or
metastatic disease.

- (2b) Have locoregionally recurrent disease not amenable to resection or radiation
therapy with curative intent or metastatic disease.

- Relapsed with radiologic evidence of progression while receiving neoadjuvant or
adjuvant endocrine therapy, with no subsequent endocrine therapy received
following progression OR

- Relapsed with radiologic evidence of progression within 1 year from completion of
adjuvant endocrine therapy, with no subsequent endocrine therapy received
following progression OR

- 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 firstline endocrine therapy for metastatic disease.
Participants may not have received more than 1 line of endocrine therapy or any
prior chemotherapy for metastatic disease OR

- Presented with de novo 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 1 line of endocrine therapy or any
prior chemotherapy for metastatic disease.

- Have postmenopausal status defined as meeting at least 1 of the following:

- Prior bilateral oophorectomy

- Age ≥60 years

- Age <60 years and amenorrheic for at least 12 months (in the absence of
chemotherapy, tamoxifen, toremifene, or ovarian suppression) and
follicle-stimulating hormone (FSH) and estradiol levels in the postmenopausal
range.

- Have 1 of the following, as defined by the Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1:

- Measurable disease

- Nonmeasurable bone-only disease. Nonmeasurable bone-only disease may include any
of the following: blastic bone lesions, lytic bone lesions without a measurable
soft tissue component, or mixed lytic-blastic bone lesions without a measurable
soft tissue component.

- Have a performance status (PS) of ≤1 on the Eastern Cooperative Oncology (ECOG) scale.

- Have adequate organ function, including:

- Hematologic: absolute neutrophil count (ANC) ≥1.5 × 109/Liter (L), platelets

≥100 × 109/L, and hemoglobin ≥8 g/deciliter (dL). Participants may receive
erythrocyte transfusions to achieve this hemoglobin level at the discretion of
the investigator; however, initial study drug treatment must not begin earlier
than the day after the erythrocyte transfusion.

- Hepatic: Total bilirubin ≤1.5 times the upper limit of normal (ULN) and alanine
aminotransferase (ALT) and aspartate aminotransferase (AST)

≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver metastases are present).

- Renal: serum creatinine ≤1.5 times ULN.

- Have discontinued previous localized radiotherapy for palliative purposes or for lytic
lesions at risk of fracture at least 2 weeks prior to randomization 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.

- Are able to swallow capsules.

- Are reliable, willing to be available for the duration of the study, and willing to
follow study procedures.

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 central nervous system (CNS) metastasis.
Screening test is not required for enrollment.

- Are currently receiving or have previously received chemotherapy for locoregionally
recurrent or metastatic breast cancer. (Note: Participants may be enrolled if they
received prior [neo]adjuvant chemotherapy for localized disease.)

- Have received prior treatment with everolimus or fulvestrant (for Cohort B only).

- Have received prior treatment with any cyclin-dependent kinases 4 and 6 (CDK4 and
CDK6) inhibitor (or participated in any CDK4 and CDK6 inhibitor clinical trial for
which treatment assignment is still blinded).

- Have initiated bisphosphonates or approved Receptor activator of nuclear factor
kappa-B ligand (RANK-L) targeted agents <7 days prior to randomization.

- Are currently enrolled in a clinical trial involving an investigational product (IP)
or non-approved use of a drug or device (other than the IP/device used in this study),
or concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study. If a participant is currently
enrolled in a clinical trial involving non-approved use of a device, then agreement
with the investigator and Eli Lilly and Company (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) live attenuated vaccines
such as yellow fever vaccine.

- Have serious preexisting medical conditions that, in the judgment of the investigator,
would preclude participation in this study (eg, 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.

- Have 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.

- Have received an autologous or allogeneic stem-cell transplant.

- Have clinical evidence of active bacterial or fungal infection or active viral
infection that, in the judgment of the investigator, would preclude participation in
this study (eg, human immunodeficiency virus [HIV] or viral hepatitis). Screening test
is not required for enrollment.