Abstract PS4-06-19: Final results of a Phase I trial of an alpha-lactalbumin (aLA) vaccine for breast cancer

Abstract Background: α-Lactalbumin (aLA) is expressed in lactating breasts and 70% of triple-negative breast cancer (TNBC) but not at other times or in other tissues. Based on the “retired protein hypothesis” vaccination with aLA provided protection from development of autochthonous tumors in transgenic murine models of breast cancer and inhibited growth of established 4T1 transplantable breast tumors in BALB/c mice. Methods: We completed accrual to a Phase I trial of recombinant human aLA with GMP-grade zymosan adjuvant in Montanide ISA 51 VG vehicle in 3 cohorts of subjects: Ia) patients with high-risk TNBC who have completed all standard treatment; Ib) patients with BRCA1, BRCA2, or PALB2 mutations who are undergoing risk-reducing mastectomies; and Ic) patients with TNBC who have residual cancer after primary chemo-immunotherapy and are receiving post-operative treatment with pembrolizumab +/- capecitabine. Three vaccinations were given once every 2 weeks. Events of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 are considered dose-limiting toxicities (DLTs). Blood was drawn prior to therapy as well as 14, 28, and 56 days after the first vaccination to assess cellular response using enzyme-linked immunosorbent spot (ELISPOT) assays of interferon-gamma and interleukin-17 production in response to aLA and for humoral response by enzyme-linked immunosorbent assay (ELISA). The breast tissue of participants in the Phase Ib cohort were or will be examined for occult lactational foci and inflammatory changes. Results: We vaccinated 26 patients in Cohort Ia, 4 in Cohort Ib, and 5 in Cohort Ic. CTCAE toxicity by dose level (DL) is summarized in Table 1 by grade for each study cohort. All adverse events (AEs) were injection site reactions, with ulceration and need for incisional drainage representing the Grade 3 DLT events. 19 of 26 patients assayed to date across all cohorts met protocol specified definitions of an immune response based on ELISPOT assays that quantify frequencies of T cells producing IFNγ or IL-17 in response to recombinant aLA; these data included 4 of 6 subjects in Cohort Ia at DL1 and 6 of 11 subjects in all cohorts treated at DL1 and tested to date. ELISPOT and ELISA data for all subjects will be available in August 2025 and will be presented. Conclusions: DL1 is the maximum tolerated dose (MTD) by protocol definition, produced at worst Grade 1 toxicity in a total of 14 of 15 subjects, and produced an immune response in most patients, based on the criteria prospectively defined in the study protocol. DL1e was tolerable in 5 of 5 subjects but was not determined the MTD per our 3+3 trial design. Immune data for all subjects in the trial, including new data across all cohorts, will be reported and will inform the design of subsequent Phase II trials. Funding Source: Department of Defense (W81XWH-17-1-0592 and W81XWH-17-1-0593). Citation Format: J. M. Johnson, E. E. Rhoades, H. B. Levengood, A. Ali, H. Gilmore, M. L. Kruse, E. E. Roesch, T. Onger, B. Elliott, E. Haury, C. Porvasnik, T. Young, T. Coutee, J. A. Fitzgerald, T. S. Stappenbeck, G. T. Budd. Final results of a Phase I trial of an alpha-lactalbumin (aLA) vaccine for breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-19.