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
Presenter: Fanni Santa, MD Session: First-in-Human Phase I Clinical Trials Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Fanni Santa 1 , Joseph Kotler 1 , Simon Chow 1 , Sharath K. Bhagavatula 1 , Vickie Y. Jo 1 , Hannah Roth 2 , Vincenzo Tarallo 1 , Samantha E. Martin 1 , Ellen Maloney 1 , Wooseok Ahn 1 , Glenn J. Hanna 2 , Oliver Jonas 1 1 Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 2 Dana-Farber Cancer Institute, Boston, MA
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 management 1 . 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 patient 2,3 . 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.
Disclosure
F. Santa, None.. J. Kotler, None.. S. Chow, None.. S. K. Bhagavatula, None.. V. Y. Jo, None.. H. Roth, None.. V. Tarallo, None.. S. E. Martin, None.. E. Maloney, None.. W. Ahn, None.. G. J. Hanna, None. O. Jonas, Kibur Medical Consultant.
Cited in
Control: 11204 · Presentation Id: 12074 · Meeting 21436