New studies test immunotherapy to boost breast cancer treatment and prevent return

Recent studies enrolling patients at Providence Cancer Institute of Oregon are investigating innovative immunotherapy combinations to improve outcomes for two challenging types of breast cancer. A new trial aims to reduce the need for chemotherapy in early-stage triple-negative breast cancer, while a second trial is testing whether combining immunotherapy with chemotherapy can reduce the risk of recurrence in high-risk, HR-positive, HER2-negative breast cancer. These studies could bring new hope to patients by offering more targeted and less toxic treatment options. Read on to find out more about both studies.  

Transforming triple-negative breast cancer treatment: A novel immunotherapy approach 

Triple-negative breast cancer (TNBC) is a particularly aggressive form of cancer that doesn’t respond to many standard therapies. This is because TNBC lacks certain proteins that are commonly targeted in other breast cancer treatments. For years, chemotherapy has been the primary treatment for TNBC, improving survival for these patients. However, it comes with certain side effects, including long-term health issues like heart damage and secondary cancers. Recently, immunotherapy has been shown to be a promising new therapeutic direction in this aggressive disease.  

An investigator-initiated study at Earle A. Chiles Research Institute, a division of Providence Cancer Institute, aims to develop a safer approach that leverages a patient’s immunity to treat early-stage TNBC. The trial is open at Providence Cancer Institute and is anticipated to open at Providence affiliate hospitals, Providence Saint John’s Cancer Institute in Los Angeles and Swedish Cancer Institute in Seattle. The principal investigator is David Page, M.D., medical oncologist at Providence Cancer Institute and associate member, Earle A. Chiles Research Institute. 

How immunotherapy is changing TNBC treatment 

Immunotherapy has reshaped cancer treatment and early trials have tested its effectiveness in TNBC. The KEYNOTE-355 study led to the FDA approval of immunotherapy for metastatic TNBC showing that combining chemotherapy with the PD-1 inhibitor pembrolizumab resulted in significantly longer survival for patients with PD-L1 positive TNBC.  

Similarly, in early-stage breast cancer, the KEYNOTE-522 study found that adding chemotherapy to pembrolizumab treatment increased the chances of a cure after surgery.  

Given the high toxicity of the current multi-agent chemotherapy regimens given to patients with early-stage TNBC, researchers are working on ways to reduce the need for chemotherapy without compromising effectiveness. This has led to the development of a novel neoadjuvant therapy that combines pembrolizumab with INBRX-106, a hexavalent OX40 agonist. INBRX-106  has shown promise in boosting T-cell activity in advanced stages of cancer. The therapy combination is designed to stimulate a more potent immune response, potentially lowering the need for chemotherapy. 

Earle A. Chiles Research Institute has played a key role in developing and evaluating OX40-targeted therapies. In particular, INBRX-106 has shown superior activity in enhancing T-cell function compared to previous therapies. As a result, researchers are moving forward with trials in patients with TNBC who have not received prior treatment to test its effectiveness in earlier stages of the disease.  

A new approach before surgery 

The phase II trial study open at Providence Cancer Institute is evaluating this combination as a neoadjuvant therapy, meaning it would be given before surgery to see if it can shrink tumors without chemotherapy. The trial uses a Simon 2-stage design. This method determines whether a treatment is promising enough to continue, while minimizing patient exposure to ineffective therapies. In the first stage, a small group of patients is treated, and if enough responses are observed the trial progresses to the second stage with a larger group. If there aren’t enough responses, the trial is stopped early. 

Researchers are hoping to see a complete response, which means no evidence of cancer remains in the tissue after treatment. If 35% of patients in the study show a complete response it would be a significant breakthrough in TNBC treatment. Importantly, if patients do not respond to the study therapy, they immediately advance to standard-of-care chemo-immunotherapy.

This trial represents a “window of opportunity” where patients with excellent response to immunotherapy alone may be given an opportunity to be cured with less or no chemotherapy.