Trial of vaccine for triple-negative breast cancer yields ‘encouraging’ results
Key takeaways:
- Most women in a phase 1 trial exhibited immune response to the vaccine.
- Injection site reactions accounted for all dose-limiting toxicities.
Nearly 75% of women treated with a novel vaccine designed to prevent triple-negative breast cancer achieved an immune response, according to updated results of a phase 1 trial.
Injection site reactions accounted for all dose-limiting toxicities, findings presented at SITC Annual Meeting showed.
“This continues to be encouraging work,” Azka Ali, MD, medical oncologist at Cleveland Clinic, told Healio. “The goal of these exploratory assays and the extension of preclinical work is to make sure that what we are doing with the vaccine is eliciting an immune response. That immune response could ultimately predict vaccine activity.”
Background and methods
The vaccine targets alpha-lactalbumin, a protein in lactating breasts that also is expressed in 70% of triple-negative breast cancer tumors.
The phase 1 trial began in 2021, and researchers have enrolled 26 patients.
Group Ia included 21 women who finished treatment for triple-negative breast cancer.
Group Ib included three women who did not have cancer but had a high risk of developing breast cancer based on presence of BRCA1, BRCA2 or PALB2 mutations and voluntarily chose to undergo preventive mastectomy.
Group Ic included two women diagnosed with early-stage triple-negative breast cancer who had residual disease after preoperative chemoimmunotherapy and surgery, and received pembrolizumab (Keytruda, Merck) with or without capecitabine.
Trial participants received three vaccinations administered once every 2 weeks.
Dose-limiting toxicities, which researchers categorized as grade 2 or worse adverse events, served as the primary endpoint.
“We set dose-limiting toxicities strictly to make sure that safety was really prioritized,” Ali said.
Ali and colleagues also evaluated response using enzyme-linked immunosorbent assays — ELISpot, which measures frequency of cytokine secretion by single cells; an assay that measured interferon gamma; and an assay that measured interleukin-17.
Results and next steps
Nearly three-quarters (73%) of participants achieved an immune response according to one of the three assays used.
Researchers determined the maximum tolerated dose to be 10 µg for alpha-lactalbumin and 10 µg for zymosan. Alternative dose combinations — including higher doses of zymosan — remain under active investigation including higher doses of zymosan.
Ali described the vaccine as “very well tolerated.”
A phase 2 trial with this vaccine is planned to begin this year.
Ali said they plan to evaluate the vaccine’s effectiveness, but more preclinical work will be done, as well.
Understanding risk factors for those who developed recurrence remains of critical importance, Ali said.
Additionally, the treatment landscape for triple-negative breast cancer has changed since researchers started testing the vaccine.
Initially, patients received chemotherapy and then went on to surgery. Now, select high-risk patients will get combination chemotherapy and immunotherapy preoperatively
“Part of the phase 2 work that’s planned right now is how to incorporate that with the evolving schema of treating early triple-negative breast cancer,” Ali said.
“Our overall long-term mission is to cut down the risk for recurrence and really cure early triple-negative breast cancer,” she added. “We’ve made quite a bit of progress from where we started to where we are today, but I would say it’s a reminder of how much work still needs to be done.”
For more information:
Azka Ali, MD, can be reached at alia22@ccf.org.
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Rhoades EE, et al. Abstract 631. Presented at: Society for Immunotherapy of Cancer Annual Meeting; Nov. 6-10, 2024; Houston.