Safety and efficacy of AIC100 chimeric antigen receptor (CAR) T-cell therapy in patients with advanced thyroid cancers: Results from the phase 1 study.
Authors: Samer Ali Srour, Victoria Meucci Villaflor, Jochen H. Lorch, Mark E. Zafereo, Sonal Gupta, Mimi I-Nan Hu, Ramona Dadu, Adam Y Lin, Yang Lu, Lori Ackatz, Melissa Cushing, Scott Avecilla, Theresa Scognamiglio, Moonsoo Jin, Janusz Puc, Gavin Liu, Karrie Du, Sebastian Alexander Mayer, Koen van Besien, Maria E. Cabanillas
Journal: Journal of Clinical Oncology (2024)

6112 Background: Patients with relapsed/refractory poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) have limited treatment options and an overall poor prognosis. Several studies highlighted the role of ICAM-1, a cell surface glycoprotein that is expressed in a variety of cancers including thyroid cancers, in tumorigenesis. AIC100 is a 3 rd generation anti ICAM-1 CAR T-cell product engineered with an affinity-tuned technology to selectively bind and kill tumor cells to improve safety, and co-expresses somatostatin receptor 2 (SSTR2) to allow CAR T-cell activity tracking by DOTATATE PET scan. We present here the results from the phase 1 dose-escalation clinical trial NCT04420754. Methods: This is a phase 1 multicenter study designed to explore 3 dose levels (DLs) of AIC100 at 1x 10 7 , 1 x 10 8 , and 5 x 10 8 , respectively. Key eligibility included adult patients (≥18 years) with ICAM-1 positive relapsed/refractory PDTC or advanced ATC who had measurable disease, and with ECOG performance status 0-2. AIC100 was infused intravenously at least 48 hours after completing lymphodepletion (Fludarabine/Cyclophosphamide x 3 days). Primary objectives included safety assessment/dose-limiting toxicities (DLTs) in the first 30 days after AIC100 infusion and to determine the recommended phase 2 dose (RP2D). Results: As of Feb 02, 2024, 15 patients were enrolled and 10 (5 ATC; 5 PDTC) were infused with AIC100 in 3 DLs. The treated patients had a median age of 55 (range, 47-69) years, were predominantly males (N=8), and with a median of 2 (range, 1-4) prior lines of therapies. Autologous AIC100 was successfully manufactured for all patients. No DLTs were observed across all DLs, and the maximum tolerated dose was not reached. Six (60%) patients developed grade 1/2 CRS. No ICANS or other serious adverse events related to AIC100 occurred. Nine patients (3 in each DL) were evaluable for efficacy analysis at day 42 after infusion; responses were assessed per study site investigators and not centrally. For all patients, the objective response rate (ORR) was 22% [1 ATC with partial response (PR) at DL2 and 1 PDTC with complete metabolic response (CR) at DL3] and the disease control rate (DCR, defined as ORR + stable disease) was 56%. For evaluable patients in DLs 2 and 3 (n=6), the ORR and DCR were 33% and 67%, respectively. Peripheral blood CAR T-cell expansion by PCR was observed in all patients. DOTATATE PET activity correlated with CAR T-cell activity and tumor responses. Conclusions: This first-in-human ICAM-1 targeted CAR T-cell study demonstrated an excellent safety profile and promising antitumor activity for AIC100 in patients with PDTC and ATC. These favorable outcomes, including a PR in DL2 and a CR in DL3, provide a proof-of-concept and support further exploration of AIC100 to optimize the RP2D and to expand for other ICAM-1-positive neoplasms. Clinical trial information: NCT04420754 .