New studies address unmet needs in treating triple-negative breast cancer

This month, we feature two clinical trials that evaluate new treatments for triple-negative breast cancer, which tends to grow and spread quickly. The first trial featured here is for patients with early-stage triple-negative breast cancer, or TNBC, who achieved a pathologic complete response – no signs of cancer – after preoperative chemotherapy in combination with pembrolizumab, a type of immune checkpoint inhibitor. The second trial will evaluate the efficacy and safety of an experimental therapy for patients with previously untreated, locally advanced, metastatic TNBC that can’t be surgically removed. 

TNBC refers to the lack of estrogen or progesterone receptors in cancer cells. Additionally, TNBC cancer cells don’t make any or too much of the protein HER2. Combined, these three conditions make TNBC difficult to treat and patients usually have a poor prognosis.  

OptimICE-pCR: Pembrolizumab vs. observation in people with TNBC 

Patients with early-stage TNBC typically respond well to preoperative chemotherapy, with pathologic complete response (pCR) rates hovering between 25-33%. Data gathered from several studies revealed that patients with TNBC who achieved pCR after preoperative chemotherapy had better disease-free survival and overall survival rates compared to patients who received chemotherapy after surgery.  

Additional studies show that combining immune checkpoint inhibitors with preoperative chemotherapy significantly improves pCR rates in patients with TNBC.  

Given the sustained survival of patients in the KEYNOTE-522 study, the combination of pembrolizumab, an immune checkpoint inhibitor, plus chemotherapy followed by 27 weeks of pembrolizumab has become standard of care for patients with stage II-III TNBC. However, in the KEYNOTE-522 study, researchers did not investigate whether it's necessary to give pembrolizumab after surgery, which can result in additional side effects and cost to the patient.

Why this study is important 

The new phase III trial, known as OptimICE-pCR, is important because it focuses on de-escalating postoperative pembrolizumab. Researchers will evaluate whether observation after surgery is as effective at preventing cancer from coming back as completing 27 more weeks of pembrolizumab after surgery.  

This is a randomized study with two groups: 

  • Group 1 will include 646-649 people who will receive 27 weeks of pembrolizumab treatment after breast surgery.  
  • Group 2 will include 646-649 people will be observed by study physicians at the beginning of the study, 12 weeks after starting the study, and 27 weeks after starting the study. This group will not receive pembrolizumab. 

Enrollment in OptimICE-pCR is through the Pacific Cancer Research Consortium. Alison Conlin, M.D., MPH, medical director, Providence Breast Cancer Medical Program and High-Risk Breast Cancer Clinic, is the principal investigator. 

Get the full study details here: 

OptimICE-PCR: De-Escalation of Therapy in Early-Stage TNBC Patients Who Achieve pCR After Neoadjuvant Chemotherapy with Checkpoint Inhibitor Therapy  

Experimental therapy RO7247669 combined with chemotherapy evaluated in new study 

In this international clinical trial, researchers will evaluate the efficacy and safety of the experimental agent RO7247669 in combination with chemotherapy. The intent of the study is to address a significant unmet medical need in patients with previously untreated, locally advanced, unresectable or metastatic PD-L1-positive TNBC who are not eligible for surgery and/or chemoradiotherapy with curative intent. 

RO7247669 in combination with the chemotherapy nab-paclitaxel will be evaluated in comparison to pembrolizumab in combination with nab-paclitaxel in patients with TNBC. Nab-paclitaxel is a standard chemotherapy agent used in treating patients with metastatic breast cancer.  

Because tumors can inhibit immunity by using the lymphocyte-activation gene 3 (LAG3) and PD-1 pathway, RO7247669 is designed to recognize, bind to and block LAG3 and PD-1 proteins. Blocking both PD-1 and LAG3 may help the immune system stop or reverse the growth of tumors. 

Pembrolizumab, as noted in the trial above, is an immune checkpoint inhibitor, a type of immunotherapy that blocks the PD-1 receptor, which also may help boost the immune system. In combination with chemotherapy, pembrolizumab is approved as a treatment for locally advanced or metastatic triple-negative, PD-L1-positive breast cancer.  

This is a two-arm, double-blind study:  

  • Group 1 will receive RO7247669 plus nab-paclitaxel. RO7247669 will be administered by intravenous infusion every three weeks. Nab-paclitaxel will be administered weekly on a repeating schedule of three weeks on followed by one week off, until disease progression or treatment discontinuation. 

  • Group 2 will receive pembrolizumab plus nab-paclitaxel. Pembrolizumab will be administered by intravenous infusion every three weeks and nabpaclitaxel will be administered weekly on a repeating schedule of three weeks on followed by one week off, until disease progression or treatment discontinuation. 

The Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, is currently enrolling patients in this trial. The principal investigator is David Page, M.D., medical oncologist at Providence Cancer Institute. Get the full study details here:  

A Study of RO7247669 + Nab-Paclitaxel Compared with Pembrolizumab + Nab-Paclitaxel in Participants with Previously Untreated, PD-L1-Positive, Locally-Advanced Unresectable or Metastatic Triple-Negative Breast Cancer 

Refer a patient 

To refer a patient to either clinical trial, contact our clinical research office:   

New research studies are added on a regular basis. To see more clinical studies, visit:  

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A multidisciplinary team of breast cancer specialists  

Providence Cancer Institute offers a comprehensive, multidisciplinary approach to breast care. Achieving optimal breast health and providing breakthrough treatments and clinical trials for people with breast cancer are equal priorities in our continuing goal to improve the health of our communities.  Learn more.  

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