The U.S. Department of Defense (DoD) has awarded Mayo Clinic researchers $11 million to conduct a Phase 2 trial investigating the TPIV110 vaccine, in combination with Herceptin (trastuzumab), as a therapy for women with HER2-positive breast cancer.
The grant was awarded to Keith L. Knutson, PhD, professor of Immunology in the Department of Immunology, and Saranya Chumsri, MD, from the Division of Hematology and Oncology at Mayo Clinic in Jacksonville, Florida.
Approximately 1 in 5 patients with breast cancer are positive for human epidermal growth factor receptor 2 (HER2). HER2-positive is a term used to describe an aggressive type of breast cancer that expresses high levels of this cell-surface protein, leading to increased tumor growth and potential to spread.
Marker Therapeutics (which merged with TapImmune in May 2018), developed its investigational vaccine, TPIV110, to target this protein in HER2-positive cancers. The vaccine consists of five selected HER2 fragments (antigens) that induce the strongest immune response against cells producing this protein.
Herceptin is a monoclonal antibody targeting HER2, blocking the signals that the protein provides for cancer cell growth and flagging cells for destruction by the immune system.
While Herceptin is already approved for several breast cancer indications, the therapy only covers 15-20% of HER2-positive breast cancers. TPIV110, however, is thought to cover 90% of these cancers and is expected to remain effective for longer periods.
The upcoming Phase 2 trial, which will include 380 women with HER2-positive breast cancer, is combining these two HER2-targeted approaches in the hope that they cover a significantly larger population.
In a Phase 1 trial (NCT01632332) with 22 HER2-positive breast cancer patients, TPIV100 — the predecessor of the current TPIV110, designed to target four HER2 antigens — was safe and well-tolerated.
Nineteen of the 22 patients (95%) showed robust T-cell responses to at least two antigens, and 75% of the patients responded to all four antigens. Moreover, patients’ immune responses were maintained months after the treatment.
“I am delighted that the U.S. Department of Defense has again chosen to support our technology and therapeutic platform with another funding commitment. This grant speaks to the strength and quality of the DoD’s relationship with Dr. Knutson and the Mayo Clinic,” Peter L. Hoang, president and CEO of Marker Therapeutics, said in a press release.
This is the second DoD grant awarded to the Mayo Clinic to study TPIV110 — in March 2017, a $3.7 million grant allowed a Phase 2 trial to test TPIV110 in women with ductal carcinoma in situ (DCIS), an early form of breast cancer that is confined to the inside of the breast milk ducts.
A second vaccine candidate, TPIV200, is also undergoing testing in a Phase 2 trial (NCT02593227) for women with triple-negative breast cancer. The trial is funded by a $13.3 million DoD grant.