Dr. Stanton on Improving Responses to Immunotherapy in Early-Stage HR+ Breast Cancer

Sasha Stanton, MD, assistant member, Cancer Immunoprevention Laboratory, Earle A. Chiles Research Institute, medical oncologist, Providence Cancer Institute, discusses efforts to improve the responses to immunotherapy regimens in early-stage hormone receptor (HR)–positive breast cancer.

Efforts to maximize the efficacy of current therapeutics by harnessing a patient’s immune response are of high interest in early-stage HR-positive breast cancer, Stanton begins. Nascent research in triple-negative breast cancer has shown an improvement in patient outcomes with immunotherapy combinations but adapting this approach to the HR-positive population has proven more challenging, she says. Patients with this disease type do not respond as well to immunotherapy, as their tumor cells interact differently with the immune microenvironment.

To address this limitation and potentially bolster Th1 immune response, researchers are conducting a 3-armed phase 1 trial (NCT04895761) in patients with Ki67-high, HR-positive, HER2-negative early-stage breast cancer, Stanton states. Notably, Ki67-high tumors are associated with poorer clinical outcomes.

The first arm was designed to assess and establish the safety of neoadjuvant therapy with the aromatase inhibitor letrazole administered in combination with the immune modulator maveropepimut-S (MVP-S, previously named DPX-Survivac) Stanton details. Previous early trials, such as the phase 1/2 DeCidE1 trial (NCT02785250), have shown that MVP-S has promising activity, was well tolerated, and produced a clinical response in patients with recurrent ovarian cancer.

The second and third arms aim to enhance immune response with the addition of radiation or intermittent low-dose cyclophosphamide to MVP-S, Stanton continues. Cyclophosphamide reduces the amount of regulatory T cells, while radiation will facilitate immunogenic cell death.

Ultimately, researchers hope to successfully adapt and expand this regimen to patients with advanced HR-positive, HER2-negative cancers, she concludes. This trial is currently in progress, and any positive signals will necessitate continued phase 2 research.