Novel CAR T-Cell Therapy Receives FDA RMAT Status in Advanced Thyroid Cancer

Results from a phase 1 trial evaluating the CAR T-cell therapy, AIC100, in relapsed/refractory thyroid cancer support the FDA’s RMAT designation.

The FDA has designated AIC100– the ICAM-1 targeting, affinity-tuned LFA-1 binder CAR T-cell therapy– for treatment in recurrent anaplastic thyroid cancer (ATC), Regenerative Medicine Advanced Therapy (RMAT) status, according to a news release published by the drug’s developer, AffyImmune.¹

Support for the designation followed interim results from a phase 1 study (NCT04420754) evaluating the safety and efficacy of AIC100 in patients with advanced thyroid cancer. The results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, with a notable instance of a complete metabolic response achieved for recurrent anaplastic thyroid cancer, which is considered the most aggressive form of the disease.²

"We believe this important recognition from the FDA further supports the therapeutic potential of AIC100 to change the current treatment paradigm in advanced thyroid cancer and potentially other forms of aggressive solid tumors," Daniel Janse, PhD, chief operating officer of AffyImmune, said in the press release. "RMAT designation was granted following the FDA’s review of safety and efficacy data from the first 10 patients dosed with AIC100 in our phase 1 study. We believe the RMAT designation reinforces the potential ability of AIC100 to meet the high unmet medical need in recurrent [anaplastic thyroid cancer], an aggressive disease where a standard of care is currently not available."

The phase 1 multicenter study evaluated AIC100 at 3 dose levels: 1 x 107, 1 x 108, and 5 x 108.³ Intravenous AIC100 was infused at least 2 days after lymphodepletion completion, composed of fludarabine and cyclophosphamide over 3 days.

A total of 17 patients were enrolled as of March 28, 2024, and 10 patients were infused with AIC100 across the 3 dose levels, including 6 with poorly differentiated thyroid cancer (PDTC) and 4 with ATC. Patients received a median of 2 (range, 1-4) prior lines of therapy and 8 had a median patient age of 55.

Primary end points included assessing the safety and tolerability of AIC100 in the aforementioned population including those who were newly diagnosed and the recommended phase 2 dose (RP2D). The secondary end points included the presence and frequency of AIC100 in the peripheral blood and tumor samples.

No DLTs were observed across all dose levels and a maximum tolerated dose was not reached. Grade 1 or 2 CRS was observed in 6 patients and no serious adverse events, including immune effector cell-associated neurotoxicity syndrome related to AIC100 infusion were reported.

At 42 days following infusion, 3 patients at each dose level (n = 9) were evaluable for efficacy, which was assessed by on-site investigators. The objective response rate (ORR) for all patients was 22% and. There was 1 partial response in a patient with anaplastic thyroid cancer at dose level 2 and 1 complete metabolic response in a patient with poorly differentiated thyroid cancer. In dose levels 2 and 3 (n = 6) the ORR and disease control rate was 33% and 67%, respectively.

The clinical trial design includes pre-screening, screening, enrollment then apheresis. Patients then went on to CAR T cell manufacturing and then AIC100 infusion. Patients were assessed for up to 12 months. In dose level 1, 3 patients were included, dose level 2 had 4 patients, and dose level 3 had 3 patients.

The study also assessed F-fluorodeoxyglucose (FDG) and 68Gallium DOTATATE PET activity. It found that this tool showed promise for in vivo tracking of CAR T cells.

Eligibility criteria for adult patients include a diagnosis for ATC BRAF wild-type at any stage, ATC BRAF mutant after failure of treatment or inability to tolerate BRAF-specific therapy, or those with PDTC who had treatment failure such as surgery, chemotherapy, radiation therapy, and/or targeted therapies.

“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,” concluded Samer Ali Srour, MD, hematologist at the MD Anderson Cancer Center and lead author of the study, and study coauthors.²

References

1. AffyImmune receives FDA Regenerative Medicine Advanced Therapy (RMAT) designation for AIC100 in recurrent anaplastic thyroid cancer. News release. AffyImmune. Published July 23, 2024. Accessed July 24, 2024. https://tinyurl.com/mwcycha2
2. 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 Oncol. 2024;42(suppl 16). doi:10.1200/JCO.2024.42.16_suppl.6112
3. Study of AIC100 CAR T Cells in relapsed/​refractory thyroid cancer. ClinicalTrials.gov. Updated July 19, 2024. Accessed July 24, 2024. https://shorturl.at/J7s6a