Abstract LB215: Safety and preliminary effects of LabVax 3(22)-23 and GM-CSF, with and without pembrolizumab, in patients with labyrinthin-expressing adenocarcinomas

Abstract Background: Labyrinthin (Lab) is a novel tumor-specific protein expressed on the cell surface of the majority of adenocarcinomas across various cancer types. LabVax 3(22)-23 contains four synthetic Lab-based peptides designed to elicit both B-cell and T-cell immune responses. We hypothesized that LabVax could elicit tumor-specific immune responses against Lab-positive adenocarcinomas. This single-institution, first-in-human phase I/II trial (UCDCC#296, NCT051013560) evaluated the feasibility and safety of LabVax 3(22)-23 and adjuvant GM-CSF in patients (pts) with Lab-positive adenocarcinomas following standard-of-care therapies. Methods: Eligible adult patients had metastatic adenocarcinomas of any histology, Lab expression on tumor cells by immunohistochemistry, adequate organ function, and a performance status of 0-1. Patients received GM-CSF subcutaneously and LabVax intradermally on weeks 1, 2, 4, 8, and 12 (Phase I) or with pembro on weeks 7, 8, 10, 13, and 19 (Phase II) in the absence of disease progression or unacceptable toxicity. The primary objective was to assess toxicity per CTCAE V5.0 in Phase I (N=10) and Phase II lead-in (N=6). Pretreatment blood samples were collected at each time point. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density gradient centrifugation and banked for functional immune cell analysis, including bulk RNA sequencing and multicolor flow cytometry as described (Ma et al. Front Immunol. 2023). Serum IgG levels against the four immune peptides were measured by ELISA. Data were collected and analyzed using the Agilent BioTek Synergy LX with Gen6 software. Results: 16 pts were enrolled: median (range) age, 52 (34-82) years; female/male, 9/7; White/Asian/Hispanic/Black/Unknown, 8/2/1/1/4; PS 1: 100%. Tumor types included colorectal (10), lung (3), ovarian (1), gastric (1), and scalp (1). Median number (range) of prior systemic therapies, 4 (1-8) cycles. Treatment was well tolerated, with no DLTs or new adverse events. OS data have not matured yet. Among the 9 pts who completed 5 doses, stable disease for ≥25 weeks was observed in 2/3 patients receiving LabVax alone and 5/6 patients receiving LabVax plus pembro. LabVax could activate T cells, B cells, monocytes, and NK cells, as shown by bulk RNA sequencing and flow cytometry analyses. The antibody levels against the different peptides varied significantly among patients, with the most common antibodies detected against peptide 1 (25%) and peptide 4 (50%). Two patients with high IgG antibody levels experienced stable disease for ∼1 year. Conclusions: LabVax and GM-CSF, either alone or in combination with pembro, were well tolerated and elicited detectable humoral and cellular immune effects in heavily pretreated patients with Lab-expressing adenocarcinomas. The study is currently accruing patients for Phase II expansion cohorts. Citation Format: Tianhong Li, Ruqiang Liang, Shuai Chen, Dennis Montoya, Siqi Long, Kit Wah Tam, Kylie Blaisdell, Leslie Garcia, Laura Molnar-McNulty, Colleen A. Pineda, Michael Babich, Primo N. Lara. Safety and preliminary effects of LabVax 3(22)-23 and GM-CSF, with and without pembrolizumab, in patients with labyrinthin-expressing adenocarcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB215.