Neoplasms

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Breast Neoplasms

Breast Diseases

Skin Diseases

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Hormones

Exemestane

Letrozole

Durvalumab

Anastrozole

Aromatase Inhibitors

Antineoplastic Agents, Immunological

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Subjects will receive standard therapy with an aromatase inhibitor (exemestane, anastrozole, or letrozole), combined with the experimental treatment of abemaciclib and durvalumab

Abemaciclib, durvalumab and aromatase inhibitor

Alison Stopeck, MD

Lea Baer, MD

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 breast cancer.

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).

Neoadjuvant Study of Abemaciclib, Durvalumab, and an Aromatase Inhibitor Early Stage Breast Cancer

A Pilot Neoadjuvant Clinical Trial of Combination Therapy With Abemaciclib, Durvalumab (MEDI4736), and an Aromatase Inhibitor in Locally Advanced Hormone Receptor Positive Breast Cancer

Change in subtype of T cell infiltrates and spatial relationship of T cells to tumor cells (number of T cells withing the tumor)

Change in number of T regs per tumor spatial unit

Change in number of myeloid derived immunosuppressive cells (M1 vs M2 macrophages) per tumor spatial unit

Change in gene expression immune signatures (RNA quantification)

The primary endpoints will be safety and tolerability of the study intervention

Pathologic response at surgery by Preoperative Endocrine Prognostic Index (PEPI) score

Pathologic response at surgery by change in Ki-67% from pre and surgical biopsies

Spots Global Cancer Trial Database for abemaciclib, durvalumab and aromatase inhibitor