AIC100 Safe, Effective for Advanced Thyroid Cancer

Samer A. Srour, MBChB, MS

Photo Credit: MD Anderson

A single infusion of the ICAM-1–targeted chimeric antigen receptor (CAR) T-cell therapy AIC100 demonstrated promising antitumor activity and a mild safety profile for patients with advanced thyroid cancers, according to results from a phase 1 dose-finding study (NCT04420754) presented at the 2024 ASCO Annual Meeting.

Across all evaluable patients and dose levels in the study (n = 9), the objective response rate (ORR) with AIC100 was 22%. For those treated with larger doses of the CAR T cells (n = 6), the ORR was 33%, suggesting a dose-response relationship and activity of the cells. At the March 2024 analysis, there had been no dose-limiting toxicity. Grade 1/2 cytokine release syndrome (CRS) was observed in 60% of treated patients and there were no cases of immune effector cell-associated neurotoxicity syndrome (ICANS).

“These findings represent a significant milestone in the development of AIC100 as a potential treatment option for patients with advanced thyroid cancers. The safety profile and promising antitumor activity observed in this phase 1 study provide a strong foundation to advance this candidate further in development,” lead investigator Samer A. Srour, MBChB, MS, assistant professor at The University of Texas MD Anderson Cancer Center, said in a statement. “We look forward to improve on these results and to further evaluate the safety and efficacy of AIC100 at higher dose levels and to potentially expand its application to other ICAM-1-positive cancers.”

In the study, patients were screened and enrolled and then underwent apheresis to collect T cells for manufacturing and cryopreserving of the CAR T cell product. Prior to administration of AIC100, patients underwent lymphodepletion using fludarabine and cyclophosphamide for 3 days. AIC100 is a third-generation CAR T-cell therapy that co-expresses ICAM-1, which is also known as CD54, and somatostatin receptor 2 (SSTR2), which allows for activity to be tracked using DOTATATE PET scan.

At the time of the poster, 6 patients with anaplastic thyroid cancer (ATC) and 4 patients with poorly differentiated thyroid cancer (PDTC) had been infused with AIC100, with an additional 7 patients with PDTC and ATC enrolled but not yet treated. Patients were evenly distributed by tumor histology across dose levels (DL). In the DL1 group, AIC100 was given at 1 x 10⁷ CAR+ cells (2 patients with ATC, 1 patient with PDTC). In DL2 group, AIC100 was given at 1 x 10⁸ CAT+ cells to 2 patients with ATC and 2 with PDTC. In DL3, AIC100 was given at 5 x 10⁸ to 2 patients with ATC and 1 with PDTC.

The median age of treated patients (n = 10) was 55 years (range, 47-69) and most were male (80%). Patients with BRAF-mutant tumors were permitted to enroll, provided they had received or were unable to receive a BRAF-targeting agent. Overall, prior to study entry, patients had received a median of 2 prior lines of therapy (range, 1-4). Response was assessed starting at day 42 post infusion of the CAR T cells, leaving 9 patients evaluable for efficacy (3 in each arm).

Of the responses, a partial response was observed in a patient with ATC who received DL2. Additionally, another patient with ATC treated at DL3 also experienced a partial response by RECIST criteria and a complete metabolic response (mCR) by FDG PET scan. There were no responses observed at DL1. When including stable disease for those treated with DL2 and DL3, the rate of disease control was 67%.

“We are excited to be the first to demonstrate the potential of autologous CAR T to induce a complete response in a patient with a solid tumor cancer," Matt Britz, chief executive offer at AffyImmune, the company developing AIC100, said in a statement. "The confirmed mCR in the AIC100 phase 1 study is the first known complete response following a single IV dose of autologous CAR T cells observed in any solid tumor cancer type."

The study continues to be ongoing, with plans to enroll 30 total patients. Additional doses are being explored beyond DL3, including one at 7.5 x 10⁸, as researchers continue to search for a recommended phase 2 dose. The study completion date is marked as December 2024.

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^{Srour SA, Villaflor VM, Lorch JH, et al. Safety and efficacy of AIC100 chimeric antigen receptor (CAR) T-cell therapy in patients with advanced thyroid cancers: Results from the phase 1 study. J Clin Onco. 2024;42 (suppl 16): 6112. Doi: 10.1200/JCO.2024.42.16_suppl.6112.}