A novel chimeric antigen receptor (CAR) T-cell therapy called AIC100, which targets the ICAM-1 protein, demonstrated encouraging responses and an acceptable safety profile in patients with two types of advanced thyroid cancer. Results from a small, first-in-human phase I trial were presented at the American Association for Cancer Research (AACR) Annual Meeting 2025 by principal investigator Samer Srour, MB ChB, Associate Professor of Stem Cell Transplantation & Cellular Therapy at The University of Texas MD Anderson Cancer Center (Abstract CT206).
The early results in anaplastic thyroid cancer (ATC) and relapsed/refractory poorly differentiated thyroid cancer (PTDC)—subtypes with limited treatment options and poor prognoses—point to progress in bringing the benefits of CAR-T cell therapies to patients with solid tumors. For nine patients receiving dose level 2 or 3, 22% were observed to have significant tumor shrinkage and 56% had control of their disease.
“The observed responses in the two dose cohorts were encouraging and provide a proof of concept for the potential of AIC100 in treating these very aggressive thyroid cancers,” Dr. Srour said. “This type of cancer is one of the deadliest and most aggressive cancers and, with current limited treatment options, most patients have a dismal prognosis of 6 months or less.”
AIC100 is a third-generation CAR T-cell therapy that works by binding to ICAM-1 on tumor cells to eliminate them. The CAR product co-expresses a protein called somatostatin receptor 2, which allows clinicians to monitor the therapy’s effectiveness with a specialized positron-emission tomography scan.
Key Results: Efficacy and Safety
Investigators enrolled 24 adult patients with newly diagnosed or relapsed/refractory ATC and relapsed/refractory PTDC with measurable disease into the multicenter trial. Fifteen patients received AIC100 as of the data cut-off on December 12, 2024. Patients had received an average of two prior lines of systemic therapy. Investigators began by evaluating three dose levels of AIC100. Patients received the therapy intravenously at least 48 hours after 3 days of standard lymphodepletion.
No responses were observed following treatment with dose level 1. Among four patients with ATC in dose levels 2 and 3, the overall objective response rate was 50%. There was one patient in the dose level 2 cohort with a partial response and one patient in the dose level 3 cohort with a complete response; both remained with no evidence of progression until 5 and 7 months from treatment, respectively. Among five patients with PDTC who received dose levels 2 and 3, the disease control rate was 60%.
No dose-limiting toxicities were observed in the initial planned three dose levels. Ten patients developed grade 1/2 cytokine-release syndrome. No serious adverse events occurred at dose levels 1, 2, and 3, and no patients developed immune effector cell–associated neurotoxicity syndrome.
Investigators also explored a fourth dose level, at which two patients developed grade 3 pneumonitis.
Based on the safety and efficacy observed, dose level 3 was selected as the recommended dose for a future phase II trial.
“These results really bring hope that we may be working toward bringing a potentially effective new treatment option for patients with thyroid cancer,” Dr. Srour said. “While it’s still early, having a complete remission and a partial response provide a strong foundation to build on, for us and for other researchers, to improve the outcomes and potentially induce durable remissions for this very aggressive disease.”
Disclosure: The trial was supported by AffyImmune Therapeutics. For full disclosures of the study authors, visit aacrjournals.org/cancerres.
