Vaccine designed to prevent triple-negative breast cancer undergoes phase 1 trial
Click Here to Manage Email Alerts
Researchers at Cleveland Clinic have initiated a first-of-its-kind study of a vaccine designed to ultimately prevent triple-negative breast cancer — the deadliest form of the disease.
The phase 1 study will determine the maximum tolerated dose of the vaccine in patients with early stage, triple-negative breast cancer and evaluate immune response to the vaccine. The FDA recently approved the vaccine as an investigational new drug, enabling Cleveland Clinic and partner Anixa Biosciences Inc. to undertake the study.
“We’re in the very first stages, and we need to study the side effects and ensure that the vaccine produces an appropriate immunologic response at a dose that we can safely give,” G. Thomas Budd, MD, of Cleveland Clinic’s Taussig Cancer Institute and principal investigator of the study, said in an interview with Healio. “But in the long term, we are optimistic that it will be useful in the preventive setting.”
Budd discussed the “retired protein hypothesis” behind the vaccine’s development and its potential value against breast cancer.
Healio: How did this vaccine come about?
Budd: This is based on work by my collaborator, Vincent Tuohy, PhD, who has developed what he calls the “retired protein hypothesis.” This postulates that there are proteins expressed by certain tissues only at certain periods of time and that tumors then aberrantly express these proteins. So, they might be a target for immunotherapy. Specifically, our trial is looking at alpha lactase albumin, which is a milk protein that’s expressed during lactation but otherwise not expressed by normal tissues. Some 70% of triple-negative breast cancers overexpress proteins.
Healio: What led to this hypothesis?
Budd: Dr. Tuohy has done a lot of prior immunologic research in multiple sclerosis and other diseases, and he happened to learn about alpha lactalbumin. He did preclinical studies that have been published in Nature Medicine showing this approach could prevent the development of breast cancer in some preclinical models. After many tries, we were able to get funding through the Department of Defense to do the current trial.
Healio: What will the trial entail?
Budd: We will immunize patients against alpha lactalbumin, so at some point after childbearing is complete, they could be immune to a large proportion of triple-negative breast cancer. Our first trial is being done in patients with triple-negative, stage II to stage III breast cancer who have completed standard treatment and are free of disease. It’s a phase 1 trial in which we’ll be giving varying doses of the vaccine every 2 weeks. We will be checking for toxicity and immune response. From this, we will determine a dose to use for future trials.
Healio: What will be the next step?
Budd: Once we get an idea of the dose, we plan to look at women who are undergoing prophylactic mastectomy due to a genetic risk for breast cancer and immunize them prior to surgery. We will look at immune response and side effects, and examine the breasts to make sure there is no evidence of inflammation that could lead to long-term side effects.
Healio: For which patients would this vaccine ultimately be indicated?
Budd: It would be indicated for people at high risk for triple-negative breast cancer, such as BRCA1 mutation carriers. Perhaps it would be suitable for PALB2 mutation carriers. Others could be at high risk, but BRCA1 would be the most obvious group. These are patients who sometimes undergo prophylactic bilateral mastectomy, which is a big operation. So, if we can prevent them from having to do that, I think this population would be well-served by the vaccine.
Healio: What is the status of the phase 1 trial?
Budd: We have accrued a few patients in this subset of individuals who have a history of triple-negative breast cancer. These patients have completed treatment but are at risk for recurrence because of microscopic metastases that could manifest as macrometastases in the future. We think this is the safest group in which to begin our investigations before going to totally healthy people.
Healio: What did preclinical studies indicate about the vaccine?
Budd: The side effects were inflammation at the injection site, as one might expect with any vaccine, and the development of breast inflammation in some animals that started to lactate. That’s why we are studying women prior to bilateral mastectomy and we’re only studying women who will not be undergoing further childbirth or lactation.
Healio: Might this be applicable to other cancers?
Budd: The retired protein hypothesis is relevant to other tumors, as well; there are other so-called retired proteins overexpressed in some cancers that might be immunologic targets in those cancers.
For more information:
G. Thomas Budd, MD, can be reached at Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195.
Perspective
Back to Top
Phase 1 trials are necessary as they often represent first in-human experience after a treatment shows promise in the preclinical setting. By definition, a phase 1 study is too small to draw any conclusions about anticancer effects. Every treatment we know to be effective in breast cancer was once in a phase 1 trial setting. Hats off to the Cleveland Clinic for mounting this trial, but time will tell if this vaccine is clinically effective in triple-negative breast cancer.
I think the precedent is set for immune responses in triple-negative breast cancers with the approval of pembrolizumab (Keytruda, Merck) in the advanced neoadjuvant settings. Studies are ongoing in other types of breast cancer.
If the vaccine works in this phase 1 trial, the primary endpoint will be generating an immune response to the vaccine. The patient population for the trial is one key component. If entry criteria include patients with heavily pretreated stage IV cancer, there is some uncertainty regarding whether the immune responses to vaccine will be robust. Then the next trial will be a phase 2 trial to establish whether the vaccine is clinically effective in the treatment of patients with triple-negative breast cancer.
The results of this trial could lead to new treatments for various types of cancer, but only after phase 1, 2 and 3 trials are completed. Many drugs don’t make it past phase 1 and phase 2 because they fail to meet their primary endpoints.
Icahn School of Medicine at Mount Sinai
Collapse
Click Here to Manage Email Alerts