The purpose of this study is to test the efficacy, safety and tolerability of a combination
of immunotherapy and anticancer drugs presurgery in patients with hormone-receptor positive
The primary hypothesis is that a Programmed death-ligand 1 (PD-L1) immune checkpoint
inhibitor combined with a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor will be well
tolerated in early stage, hormone receptor positive (HR+) breast cancer patients treated with
neoadjuvant endocrine therapy (NET). The secondary hypothesis and biomarker based endpoint is
that patients with HR positive locally advanced breast cancer with low to intermediate
stromal tumor-infiltrating lymphocytes (TILs) will demonstrate an increase in stromal TILs
following NET when combined with abemaciclib and durvalumab for 4 cycles (16 weeks).
1. A signed, written informed consent will be obtained from the subject prior to
performing any protocol-related procedures, including screening evaluations.
2. Postmenopausal women age ≥ 18 years at time of study entry. Women will be considered
post-menopausal if they have been amenorrheic for 12 months without an alternative
medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of exogenous hormonal
treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical
sterilization (bilateral oophorectomy or hysterectomy).
- Women <50 years of age receiving luteinising hormone-releasing hormone (LHRH)
agonist for ovarian suppression are also eligible for the study but must initiate
LHRH agonist therapy at least 2 weeks prior to starting on study intervention.
- Women ≥ 50 years of age would be considered post-menopausal if they have been
amenorrheic for 12 months or more following cessation of all exogenous hormonal
treatments, had radiation-induced menopause with last menses >1 year ago, had
chemotherapy-induced menopause with last menses >1 year ago, or underwent
surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
3. Histologically confirmed estrogen and/or progesterone positive invasive breast cancer,
defined as either estrogen and/or progesterone receptor (ER/PR) staining >10%, AND
Human Epidermal Growth Factor Receptor 2 (HER2) negative by either
Immunohistochemistry (IHC) or Fluorescent in situ Hybridization (FISH).
4. Clinical stage II-III disease with no clinical or radiologic evidence of metastatic
disease. Patients must have a measurable primary breast lesion as per Response
Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
5. Eastern Cooperative Oncology Group (ECOG) status < 1.
6. Patient must be able to swallow pills.
7. Adequate organ and marrow function as defined below and in Table 1:
- Hemoglobin ≥ 9 g/deciliter
- Absolute neutrophil count ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 ×
institutional upper limit of normal (ULN)
- Bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected Gilbert's disease,
bilirubin ≤ 2 × ULN
- Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation,
or creatinine ≤1.5 x ULN
8. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
9. Must have a life expectancy of at least 12 weeks.
1. Any serious preexisting medical condition(s) that would place the patient at increased
risk for toxicities including interstitial lung disease, severe dyspnea at rest or
requiring oxygen therapy, history of major surgical resection involving the stomach or
2. Body weight < 30 kg (or 66.5 lbs.). If during the study, the patient's weight drops to
< 30 Kg (or 66.5 lbs), they will be withdrawn from the study.
3. Females who are pregnant or lactating.
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis,
or psychiatric illness/social situations that would limit compliance with study
requirement or compromise the ability of the subject to give written informed consent
5. Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring
systemic treatment (within the past 2 years) are eligible
6. History of significant cardiac disease including heart failure, ventricular
arrhythmia, or prolonged QT syndrome.
7. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis, or a preexisting chronic condition resulting in baseline ≥ Grade 2
8. History of primary immunodeficiency, or subjects who are known to be HIV (Human
Immunodeficiency Virus ) positive
9. History of organ transplant that requires use of immunosuppressives
10. Known allergy or reaction to any of the study drugs.
11. Other invasive malignancy within 2 years except for noninvasive malignancies such as
cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma
in situ of the breast that has/have been surgically cured
12. Major surgical procedure (as defined by the investigator) within 30 days prior to the
first dose of study drugs or still recovering from prior surgery
13. Known history of tuberculosis
14. Subjects who are known to be hepatitis B or C positive
15. History of prior therapy with a checkpoint (PD-L1/PD-1) including durvalumab or CDK4/6
16. History of prior ipsilateral radiation therapy to the cancer-affected breast
17. History of prior therapy with an investigational anticancer therapy within 6 weeks
prior to the first dose of study drugs
18. Prior chemotherapy or aromatase inhibitor therapy for breast cancer
19. Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab, with the exceptions of intranasal, topical, and inhaled
corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10
mg/day of prednisone or equivalent
20. Patients who must take strong cytochrome cytochrome P450 (CYP3A) inhibitors such as
clarithromycin, diltiazem, verapamil, itraconazole, or ketoconazole
21. Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab
22. Concurrent enrollment in another therapeutic clinical study