Abstract CT056: Phase I study of intratumoral microdevices reveals heterogenous immune and apoptotic responses across distinct drug-treated regions in adenoid cystic carcinoma of the head and neck

Abstract Background: Adenoid cystic carcinoma (ACC) is a salivary or glandular cancer that is frequently resistant to systemic therapies. Rarity and disease heterogeneity limit drug-response assessment and complicate management1. Implantable microdevices (IMD) have demonstrated safety and feasibility in solid tumors, allowing localized drug delivery and in-situ assessment of tumor responses to 20 therapeutic agents in parallel per patient2,3. This Phase I study aims to evaluate IMD-feasibility and explore tumor-specific responses in ACC to mechanistically distinct anticancer agents (NCT05553782). Methods: The study enrolled patients with primary ACC arising in the head and neck undergoing definitive surgery. Intratumoral microdevices (IMDs) were implanted to deliver ∼15 anticancer drugs at nanoconcentrations, including chemotherapeutics, targeted agents, and immunotherapies. The IMDs remained in the patients’ tumors for three days and were retrieved at standard surgery. Resected tumor-IMD specimens underwent multimodal analysis, including histopathology, cleaved caspase-3 (CC3) immunohistochemistry to assess apoptosis, cyclic immunofluorescence (CycIF), and spatial transcriptomic (ST) profiling. Results: To date, five patients have been enrolled to the study. A total of 14 devices (average 2.8 per patient) were implanted with a median retrieval of 2 IMDs/patients. Device loss occurred in only one patient during gross sectioning. No serious adverse events were observed. Across the cohort, apoptotic index (CC3%) had the highest average with ATRA (44.1%), enfortumab vedotin (41.7%), vinorelbine (40.9%), venetoclax (39.4%), and pembrolizumab (38.9%); lowest with 5-FU (21%), and ipilimumab (20.1%). CycIF analysis revealed increased infiltration of CD8+ cytotoxic T cells (CD3+; CD8+, GzmB+) with ATRA, sacitizumab and enfortumab vedotin. Regions treated with doxorubicin, 5-FU, carboplatin, and ipilimumab showed higher CD163 expression, suggesting a more suppressive myeloid-dominant microenvironment. ST revealed heterogeneous pathway activity across drug-treated regions, including ATRA with increased immune and apoptosis-related signaling, and p53 pathway upregulation with venetoclax. Conclusions: IMD implantation and retrieval were feasible and reproducible across patients. Across primary ACC, microdevice-delivered ATRA, enfortumab vedotin, and sacitizumab were associated with more robust apoptosis-inducing effect and CD8+ T cell enrichment, whereas 5-FU, ipilimumab, and docetaxel exhibited tumor-associated macrophage enrichment. These findings may guide prioritization of candidate drugs or combinations, and personalization of therapy.References:1.Fang et al, Oral Oncol. 2022 Jul;130:105945.2.Peruzzi et al, Sci Transl Med. 2023 Sep 6;15(712):eadi0069.3.Dominas et al, IEEE Trans Biomed Eng. 2022 Jan;69(1):412-421. Citation Format: Fanni Santa, Joseph Kotler, Simon Chow, Sharath K. Bhagavatula, Vickie Y. Jo, Hannah Roth, Vincenzo Tarallo, Samantha E. Martin, Ellen Maloney, Wooseok Ahn, Glenn J. Hanna, Oliver Jonas. Phase I study of intratumoral microdevices reveals heterogenous immune and apoptotic responses across distinct drug-treated regions in adenoid cystic carcinoma of the head and neck [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT056.