FDA clears way for Cleveland Clinic’s groundbreaking breast cancer vaccine

FDA clears way for Cleveland Clinic’s groundbreaking breast cancer vaccine

Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Triple-Negative Breast Cancer

Study Design

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Inclusion Criteria:

• Histologically proven invasive breast cancer.

• Primary tumor must be ER-negative (ER in <1% of cells), PR-negative (PR in <1% of cells), and HER2-negative (0-1+ by IHC or FISH ratio<2.0 with signal number <6/cell). 4.1.3 Patients must be high risk, defined as either:

  • Pathologic stage IIA, IIB, IIIA, IIIB, or IIIC by AJCC 8, or

  • Residual invasive cancer in breast or regional nodes following preoperative chemotherapy.

    • 1 months since last active therapy (chemotherapy, radiation therapy, or surgery) and <36 months since the initiation of treatment for the current cancer, based on the period of highest risk for patients with Stages I-III triple-negative breast cancer
• Treatment prior to enrollment must be consistent with contemporary NCCN guidelines, found at: https://www.nccn.org/
• ECOG Performance Status 0-1

• Adequate major organ function, defined as:

  • WBC > 3,000/mcl,
  • hemoglobin > 10.0 gm/dL,
  • platelets > 100,000/mcL,
  • total bilirubin within normal limits,
  • ALT/AST <3 x upper limits of normal (ULN),
  • serum creatinine < 1.5 x ULN
• Serum prolactin level must be < upper limits of normal (ULN);
• Participants must have the ability to understand and the willingness to sign and provide a written informed consent document;
• Participants must have archival tissue available for potential correlative studies (e.g., assays for α-lactalbumin expression or tumor infiltrating lymphocytes), but tumors will not be required to exhibit overexpression of α-lactalbumin for enrollment.
• Participants agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection

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Cleveland Clinic researchers have launched the next step in their novel study of a vaccine aimed at preventing triple-negative breast cancer, the most aggressive and lethal form of the disease.

Funded by the U.S. Department of Defense, the new phase 1b study will enroll cancer-free individuals at high risk for developing breast cancer who have decided to voluntarily undergo prophylactic mastectomy to lower their risk.

Individuals in that category typically carry genetic mutations that put them at risk of developing triple-negative breast cancer or have high familial risk for any breast cancer. The study, conducted at Cleveland Clinic's main campus, will evaluate safety and monitor immune response.

The new study will include approximately 6-12 patients and is anticipated to be complete by the end of 2023. Study participants will receive three vaccinations given two weeks apart and will be closely monitored for side effects and immune response.

The phase 1b clinical trial, conducted in partnership with Anixa Biosciences, Inc., follows the ongoing phase 1a study, which opened in 2021 and is expected to be complete in the 4^th quarter of 2023. The phase 1a trial includes patients who completed treatment for early-stage, triple-negative breast cancer within the past three years and are currently tumor-free but at high risk for recurrence.

Triple-negative breast cancer is the form of the disease for which we have the least effective treatments. Long term, we are hoping that this can be a true preventive vaccine that would be administered to cancer-free individuals to prevent them from developing this highly aggressive disease.".

G. Thomas Budd, M.D., of Cleveland Clinic's Taussig Cancer Institute and principal investigator of the study

According to Dr. Budd, there is a great need for improved treatments for triple-negative breast cancer, which does not have biological characteristics that typically respond to hormonal or targeted therapies. Despite representing only about 12% to 15% of all breast cancers, triple-negative breast cancer accounts for a disproportionately higher percentage of breast cancer deaths. It is twice as likely to occur in Black women, and approximately 70 to 80% of the breast tumors that occur in women with mutations in the BRCA1 gene are triple-negative breast cancer.

The vaccine is based on pre-clinical research led by the late Vincent Tuohy, Ph.D., who was the Mort and Iris November Distinguished Chair in Innovative Breast Cancer Research at Cleveland Clinic's Lerner Research Institute. Dr. Tuohy was an outstanding and passionate scientist and his decades of groundbreaking research led to the development of this investigational vaccine.

The vaccine targets a lactation protein, α-lactalbumin, which is no longer found after lactation in normal, aging tissues but is present in the majority of triple-negative breast cancers. If breast cancer develops, the vaccine is designed to prompt the immune system to attack the tumor and keep it from growing.

The study is based on Dr. Tuohy's research that showed that activating the immune system against α-lactalbumin was safe and effective in preventing breast tumors in mice. The research, originally published in Nature Medicine, was funded in part by philanthropic gifts from more than 20,000 people over the last 12 years.

"It was Dr. Tuohy's hope that this vaccine would demonstrate the potential of immunization as a new way to control breast cancer, and that a similar approach could someday be applied to other types of malignancy," added Dr. Budd.

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Is a Preventive Breast Cancer Vaccine in Our Future?

What is the focus of the new phase of the clinical trial?

The vaccine study’s second phase will focus on cancer-free individuals who:

• Are at high risk for developing breast cancer.
• Have opted to undergo a prophylactic mastectomy to lower breast cancer risk.

People in this group typically carry genetic mutations that put them at risk of developing TNBC or they have a family history of breast cancer.

Six to 12 patients will be included in this trial phase. Participants will receive three vaccinations given two weeks apart. Their immune system response will be closely monitored, and they’ll undergo blood tests and physical exams to make sure there are no undue side effects.

The expectation is to complete this portion of the clinical trial by the end of 2023. This phase is being funded by the U.S. Department of Defense and conducted in partnership with Anixa Biosciences, Inc. (Cleveland Clinic licensed the vaccine technology to Anixa Biosciences.)

The U.S. Food and Drug Administration (FDA) approved an investigational new drug application for the vaccine, allowing the clinical trial to move forward.

Is the first phase of the trial complete?

Not yet, but it should be done by the end of 2023. This phase, which began two years ago, focused on individuals who have completed treatment for TNBC and are at risk of their cancer returning.

The goal of the phase-one trial is to determine the proper dosage in patients with early-stage TNBC and to optimize the body’s immune response to the vaccine.

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