Abstract OT3-02-03: IMMUNe mOdulation in early stage estrogen receptor positive breast cancer treated with neoADjuvant Avelumab, Palbociclib, and Tamoxifen: The ImmunoADAPT study (NCT03573648)

Background: While some patients with early stage endocrine receptor positive (ER+) breast cancer experience excellent prognosis, a subset of patients with more aggressive phenotypes still have a high rate of recurrence despite optimal adjuvant endocrine therapy and chemotherapy, thus novel therapies are needed for patients with high risk disease. Although immune checkpoint blockade has shown significant benefit in numerous types of cancer, initial reports demonstrate low response rates to single agent programmed cell death ligand 1 (PD-L1) inhibition in ER+ breast cancer. Inhibitors of cyclin dependent kinases (CDK) 4 and 6 in combination with endocrine therapy are highly active in breast cancer, and recently have been demonstrated to recruit immune cells, and increase PD-L1 on tumor cells in preclinical models. Increased tumor infiltrating lymphocytes (TILs) has been observed with neoadjuvant treatment with CDK4/6 inhibitors in patients with ER+ breast cancer. We thus hypothesize that the addition of palbociclib (CDK4/6 inhibitor) will improve responses to avelumab (PD-L1) inhibitor in patients with high risk ER+ breast cancer. Trial Design: Eligible participants are those stage II or III ER+HER2- breast cancer (T2N0 must have ≥grade 2, T1N+ must have at least a 1.5cm breast primary). Patients will undergo a baseline MRI and biopsy, start tamoxifen +/- palbociclib for 1 cycle (1 cycle =28 days), and then undergo a repeat MRI and biopsy. Avelumab will be added to both arms in cycle 2. Patients will be treated for 3 cycles of avelumab with tamoxifen +/- palbociclib (thus 4 cycles total, including run-in without avelumab). Patients will be treated as long as there is no evidence of progression and therapy is tolerated, and then undergo MRI and surgery. The primary objective is to determine the clinical complete response (cCR) rate by MRI. Secondary objectives include evaluation of TILs (HE 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT3-02-03.