AffyImmune Therapeutics’ CAR-T AIC100 Shows Promise in Thyroid Cancers

AffyImmune Therapeutics’ AIC100, an investigational chimeric antigen receptor T-cell (CAR-T) therapy being evaluated for the treatment of anaplastic (ATC) and poorly differentiated (PDTC) thyroid cancers, has shown encouraging safety and efficacy in data from a phase 1 clinical trial (NCT04420754).¹ The results are being presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Samer Ali Srour, MBChB, MS, an assistant professor in the Department of Stem Cell Transplantation, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center, in Houston, Texas.

AIC100 has micromolar affinity for ICAM-1, which is overexpressed in many cases of ATC and PDTC. Among 6 patients who were treated with AIC100 as of the February 14, 2023, data cutoff, 3 patients treated at dose-level 1 (1x10⁷ CAR T-cells; DL1) and 1 patient treated at DL2 (1x10⁸ CAR T-cells) were evaluable for efficacy. The trial design utilized fluorodeoxyglucose (FDG) PET/CT scans to assess responses and DOTATATE PET/CT scans to track the distribution and expansion of the CAR-T, which coexpresses somatostatin receptor 2.

One patient with relapsed ATC, who was treated at DL2 and was evaluated at 42 days posttreatment, had achieved a partial response (PR) with a 42% reduction in target tumor lesion.¹ It was additionally noted that this patient’s PR was maintained at 3 months and that 14 days following CAR-T infusion, increased DOTATE avidity was observed on the DOTATATE PET/CT scan. Another patient, who has PDTC and was treated at DL1, showed stable disease. It was noted that reduced FDG activity correlating with higher activity in the DOATATE scan was observed in PET scans for this patient. According to a May 25, 2023, press release from AffyImmune Therapeutics, a seventh patient treated in the trial, who received DL2, also showed tumor reductions at 42 days posttreatment.²

“We are very encouraged by the early data, as it marks a groundbreaking CAR-T patient response in aggressive and difficult to treat anaplastic thyroid cancers,” Matt Britz, the chief operating officer of AffyImmune, said in the statement.² “This is an important clinical milestone for AffyImmune as we continue to develop AIC100 in the clinic and explore additional solid tumor indications with high unmet need.”

In terms of safety, it was noted that there were no dose-limiting toxicities (DLTs) or serious adverse events (AEs) observed among the treated patients as of February 14, 2023.¹ Cases of grade 1 cytokine release syndrome were reported in 2 patients. There we no cases of immune effector cell-associated neurotoxicity syndrome observed. Srour and colleagues noted that 1 of the patients treated at DL2 could not be evaluated because they withdrew from the study early as a result of disease-related toxicity and the other patient treated at DL2 had not yet reached the end of the DLT period at this time.

“The objective partial response in DL2 for a patient with metastatic ATC who failed multiple lines of therapy is unprecedented and very encouraging,” Srour added to the statement.² “AIC100 demonstrated an excellent safety profile with no DLTs in patients with ATC and PDTC, and the antitumor activity is promising, especially these responses [that] were observed at the low dose levels 1 and 2.”

REFERENCES
1. Srour SA, Cabanillas ME, Gupta S, et al. Safety and early efficacy results of phase 1 study of affinity tuned and trackable AIC100 CAR T cells in ICAM-1 positive relapsed and/or refractory advanced poorly differentiated and anaplastic thyroid cancers. Presented at: the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. Abstract #6095
2. Affyimmune Therapeutics announces positive safety and early efficacy results from phase 1 study of AIC100 CAR T cells in anaplastic and advanced thyroid cancers at 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. News release. AffyImmune Therapeutics, Inc. May 25, 2023. Accessed June 2, 2023. https://affyimmune.com/recent/affyimmune-therapeutics-announces-positive-safety-and-early-efficacy-results-from-phase-1-study-of-aic100-car-t-cells-in-anaplastic-and-advanced-thyroid-cancers-at-2023-american-society-of-clinical-on/