A novel chimeric antigen receptor (CAR) T-cell therapy targeting the ICAM-1 protein has shown encouraging responses in patients with advanced thyroid cancers, according to results presented at the American Association for Cancer Research (AACR) Annual Meeting 2025.
The first-in-human phase I trial of AIC100, led by Dr. Samer Srour from The University of Texas MD Anderson Cancer Center, demonstrated both efficacy and an acceptable safety profile in patients with anaplastic thyroid cancer (ATC) and relapsed/refractory poorly differentiated thyroid cancer (PTDC) – two aggressive subtypes with limited treatment options and poor prognoses.
"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," said Dr. Srour, Associate Professor of Stem Cell Transplantation & Cellular Therapy at MD Anderson. "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."
Promising Efficacy in Advanced Disease
The multicenter trial enrolled 24 adult patients with newly diagnosed or relapsed/refractory ATC and relapsed/refractory PTDC with measurable disease. Fifteen patients received AIC100 as of the December 12, 2024 data cutoff. Patients had received an average of two prior lines of systemic therapy.
While no responses were observed at the lowest dose level (dose level 1), the results became more encouraging at higher doses:
- Among four ATC patients receiving dose levels 2 and 3, the overall objective response rate was 50%
- One patient in dose level 2 achieved a partial response
- One patient in dose level 3 achieved a complete response
- Both responding patients remained progression-free at 5 and 7 months post-treatment, respectively
- Among five PTDC patients at dose levels 2 and 3, the disease control rate was 60%
Overall, for nine patients receiving dose level 2 or 3, 22% experienced significant tumor shrinkage and 56% achieved disease control.
Safety Profile and Mechanism of Action
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 somatostatin receptor 2, allowing clinicians to monitor the therapy's effectiveness with specialized positron emission tomography (PET) scans.
The safety profile was encouraging at the first three dose levels:
- No dose-limiting toxicities were observed
- Ten patients developed grade 1/2 cytokine release syndrome (CRS)
- No serious adverse events occurred
- No patients developed immune effector cell-associated neurotoxicity syndrome (ICANS)
When investigators explored a fourth, higher dose level, two patients developed grade 3 pneumonitis. Based on the combined safety and efficacy data, dose level 3 was selected as the recommended dose for future phase II trials.
Advancing CAR T-Cell Therapy for Solid Tumors
This trial represents important progress in extending CAR T-cell therapy, which has revolutionized treatment for certain blood cancers, to solid tumors – an area that has proven more challenging.
"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 noted. "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."
The trial was supported by AffyImmune Therapeutics, the developer of AIC100. The therapy's ability to target ICAM-1, a protein expressed on many cancer cells, suggests potential applications beyond thyroid cancer if further studies continue to show positive results.
For patients with ATC in particular, who face extremely limited treatment options and typically survive less than six months after diagnosis, these early results offer a glimmer of hope in an otherwise bleak therapeutic landscape.
