Roswell Park Clinical Trial Points Toward Promising New Therapy for Most Aggressive Type of Breast Cancer

High rate of complete remission achieved without immune-related adverse side effects in patients with TNBC

• Triple-negative breast cancer accounts for 10-20% of all breast cancers

• Study assessed a new pre-surgery immunotherapy/chemotherapy combination

• Findings appear in Journal for ImmunoTherapy of Cancer

A new treatment approach developed at Roswell Park Comprehensive Cancer Center has shown promising results in a phase 1 clinical trial for patients with triple-negative breast cancer (TNBC), the most aggressive type of breast cancer. Results of the study are newly reported in The Journal for ImmunoTherapy of Cancer.

Conducted exclusively at Roswell Park and led by clinical principal investigator Shipra Gandhi, MD, Associate Professor of Oncology in the Department of Medicine at Roswell Park, the clinical trial enrolled nine patients with early-stage TNBC. TNBC accounts for 10-20% of all breast cancers and, compared to other breast cancer types, is associated with a high mortality rate, even when diagnosed in the early stages.

Five of nine patients enrolled in the study achieved complete remission and another patient achieved near-complete remission, for a total of approximately 66%. That’s comparable to outcomes for patients who receive a different treatment combination already in use, but the Roswell Park regimen appears promising because patients did not experience any immune-related adverse events, which can be serious and sometimes fatal.

“We are very excited with these promising results from our study of a new treatment combination for patients with this most highly aggressive form of breast cancer, triple-negative breast cancer,” says Dr. Gandhi, a medical oncologist and staff physician at Roswell Park. “Because this initial study was in a small number of patients, it will be important to validate these findings in a larger study.”

Patients in the clinical trial received neoadjuvant chemotherapy, which is given to shrink the tumor before surgery. The treatment combined paclitaxel (brand name Taxol), a chemotherapy drug, along with a type of immunotherapy called a chemokine modulatory regimen (CKM). Both work by preventing tumor cells from growing. The CKM therapy included the drugs rintatolimod (brand name Ampligen), interferon alfa-2b (brand name Intron A) and celecoxib (brand name Celebrex). Patients also received the chemotherapy drugs doxorubicin (brand name Adriamycin), which kills cancer cells, and cyclophosphamide (brand name Cytoxan), which stops their growth.

The current standard regimen that combines neoadjuvant chemotherapy with the immunotherapy pembrolizumab (brand name Keytruda) can produce the same rate of complete remission, but it also increases the risk of immune-related adverse events.

Pawel Kalinski, MD, PhD, Professor of Immunology and Chief of Translational Immuno-Oncology at Roswell Park, served as scientific lead of the research and principal investigator of the National Cancer Institute (NCI) program project grant P01CA234212.

The study was informed by the observation that following neoadjuvant chemotherapy, higher numbers of cytotoxic T lymphocytes (CTLs) — cancer-killing immune cells — in a patient’s tumor tend to predict a greater likelihood of complete remission. The team showed that administering rintatolimod and interferon alpha together raised the level of beneficial chemokines that attract CTLs while suppressing  undesirable chemokines that attract regulatory T cells (Tregs), which limit the immune system’s tumor-fighting power. Their work also demonstrated that the CKM regimen triggered production of beneficial chemokines in tumor tissue but not in healthy tissue. The clinical trial results reflected the results of the preclinical work; patients’ tumors contained higher numbers of CTLs after the chemotherapy/immunotherapy combination was administered.

Florida-based biopharmaceutical company AIM ImmunoTech Inc. supplied the rintatolimod for use in this study.

From the world’s first chemotherapy research to the PSA prostate cancer biomarker, Roswell Park Comprehensive Cancer Center generates innovations that shape how cancer is detected, treated and prevented worldwide. Driven to eliminate cancer’s grip on humanity, the Roswell Park team of 4,000 makes compassionate, patient-centered cancer care and services accessible across New York State and beyond. Founded in 1898, Roswell Park was among the first three cancer centers nationwide to become a National Cancer Institute-designated comprehensive cancer center and is the only one to hold this designation in Upstate New York. To learn more about Roswell Park Comprehensive Cancer Center and the Roswell Park Care Network, visit www.roswellpark.org, call 1-800-ROSWELL (1-800-767-9355) or email ASKRoswell@RoswellPark.org.