Abstract 3035: Phase I trial of alpha-lactalbumin vaccine in high-risk operable triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) has a poor prognosis and may be associated with germline mutations. α-lactalbumin (aLA) is expressed in lactating breasts but not at other times or in other tissues. Expression of aLA is found in 70% of TNBC (PMID: 27322324) so could be an immunologic target for TNBC based on the “retired protein hypothesis” (PMID: 31926646). In pre-clinical studies vaccination with aLA inhibited growth of established breast tumors and provided protection from development of autochthonous tumors in transgenic murine models of breast cancer and against 4T1 transplantable breast cancer in BALB/c mice (PMID: 20512124). Methods: To determine the safety and immunogenicity of aLA, patients with early stage TNBC are being entered in a Phase I trial of aLA with GMP-grade zymosan adjuvant in Montanide ISA 51 VG vehicle. Subjects receive 3 vaccinations given once every 2 weeks. Events of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 are considered dose-limiting toxicities (DLTs). Results: CTCAE toxicity by dose level is summarized below. All DLTs were injection site reactions, with ulceration and need for incisional drainage representing the grade 3 events. ELISpot assays to determine frequencies of T-cells producing IFN-γ and IL-17 in response to recombinant aLA and ELISA assays of antibody response to aLA will be available in December 2022. Conclusion: Dose level 2 appears to be the maximum tolerated dose. Accrual to dose levels 1 and 2 will be expanded to further define toxicity and immunologic effects. Accrual of patients with BRCA1 or PALB2 mutations planning to undergo prophylactic mastectomy is beginning in order to define the toxicity and immunologic effects in this group and to determine whether inflammatory changes from occult lactational foci will be produced. Funding Source: Department of Defense (W81XWH-17-1-0592 and W81XWH-17-1-0593) Worst Toxicity by Dose Level Dose Level aLAC (mcg) dose Zymosan (mcg) dose n Patients n Grade 0 n Grade 1 n Grade 2 n Grade 3 1 10 10 3 3 2 100 10 3 3 3 500 10 3 2 1 Original 2 100 100 1 1 Citation Format: George Thomas Budd, Justin M. Johnson, Emily Rhoades, Halle Moore, Holly Levengood, Megan Kruse, Erin Roesch, Jame Abraham, Brenna Elliott, Elena Haury, Rachel Swartz, Holly Pederson, Zahraa Al Hilli, Vincent Tuohy. Phase I trial of alpha-lactalbumin vaccine in high-risk operable triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3035.