Cleveland Clinic researchers identified the maximum tolerated dose of an alpha-lactalbumin vaccine in a Phase 1 trial involving patients with triple-negative breast cancer and those at genetic risk for triple-negative breast cancer. The vaccine elicited immune responses in 12 of 16 evaluated patients at dose level 1, including 4 of 6 subjects at the maximum tolerated dose, according to findings presented in a recent abstract published in the Journal for ImmunoTherapy of Cancer.
The trial (NCT04674306) enrolled 26 participants across three groups: 21 patients with high-risk triple-negative breast cancer (TNBC) who completed standard treatment (Group 1A), 3 TNBC patients with residual cancer post-chemo-immunotherapy receiving pembrolizumab with or without capecitabine (Group 1C), and 2 patients with BRCA1, BRCA2, or PALB2 mutations undergoing risk-reducing mastectomies (Group 1B).
The vaccine utilized recombinant human alpha-lactalbumin with a GMP-grade zymosan adjuvant in a Montanide ISA 51 VG vehicle. Participants received three vaccinations at 2-week intervals. The researchers selected alpha-lactalbumin as the target based on its expression in 70% of TNBC cases and lactating breast tissue.
In preclinical studies, the vaccine demonstrated protection from tumor development in transgenic murine models and inhibited the growth of established 4T1 transplantable breast tumors in BALB/c mice.
Immune responses were measured via ELISpot assays, quantifying T cells producing IFNγ and/or IL-17 in response to recombinant alpha-lactalbumin. Adverse events, defined as Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2, were primarily injection site reactions, with some Grade 3 events manifesting as ulceration requiring incisional drainage.
While the trial will provide immune response data for additional subjects by August 2024, the investigators noted that this Phase 1 study was not powered to assess clinical efficacy, which will require evaluation in Phase 2 trials.
The research team was led by Emily E. Rhoades, MD, and colleagues at the Cleveland Clinic Foundation.
