Abstract A002: Analysis of tumor microenvironments in ovarian cancer patients receiving anti-BTN1A1 immunotherapy combined with standard-of-care therapy

Abstract

Abstract Background Immune checkpoints have emerged as key regulators of the immune responses against various tumor types. Butyrophilin 1A1 (BTN1A1) has been identified as a novel immune checkpoint protein that has the potential to be targeted for new immunotherapeutic treatment options. We have observed that BTN1A1 and PD-L1 expression are mutually exclusive in various human solid tumors. Recently, Nelmastobart (BTN1A1-targeting antibody, hSTC810) has successfully completed phase 1 clinical trials. To ensure the effectiveness of Nelmastobart, it is crucial to possess a profound comprehension of patients’ tumor microenvironment factors involved. Here, we report Opal multiplex immunofluorescence and Hyperion imaging mass cytometry approach that includes a deeper understanding of the spatial relationships in the tumor microenvironment. Methods In a first-of-its-kind Phase 1 clinical trial, we are to characterize the safety profile and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Nelmastobart is administered as monotherapy at increasing dose levels of 0.3, 1, 3, 6, 10, and 15 mg/kg on a Q2W schedule. To understand the heterogeneity of the interaction mechanisms between immune cells and cancer cells, Patients’ FFPE specimens were stained cancer and immune cells using Opal multiplex immunofluorescence and analyzed Hyperion imaging mass cytometer. Results We enrolled 45 pts with various cancers in a phase I trial of anti-BTN1A1, a novel immunotherapy. We tested doses from 0.3 to 15 mg/kg and found no DLTs. We report results for ovarian cancer. Opal multiplex immunofluorescence analysis showed that anti-BTN1A1 therapy increased the infiltration and activation of CD8+ T cells and NK cells and decreased the level of regulatory T cells in the tumor microenvironment. We also found the opposite expression of BTN1A1 in PD-L1-expressing cancer cells in KI67-negative tumors from ovarian cancer patients. Conclusions Nelmastobart treatment activates immune response pathways and enhances anti-tumor activity with anti-PD-L1 combination therapy in vitro, in vivo, and clinical settings. The results of the study suggest that BTN1A1 is a novel immune checkpoint that can be targeted to overcome resistance to conventional therapies in cancer patients. Citation Format: Stephen S Yoo, Youngseung Kim, Seung Hoon Lee, Soohyeon Lee, Sangjoon Shin, Patricia LoRusso, Hyunjin Jung, David Hong. Analysis of tumor microenvironments in ovarian cancer patients receiving anti-BTN1A1 immunotherapy combined with standard-of-care therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr A002.