A non-randomized, open-label trial of AIC100, an autologous chimeric antigen receptor T-cell agent for the treatment of relapsed/refractory thyroid cancer, is currently recruiting patients at the Weill Cornell Medical College in New York, under the supervision of Koen van Besien, MD, PhD.
A non-randomized, open-label trial of AIC100, an autologous chimeric antigen receptor (CAR) T-cell agent for the treatment of relapsed/refractory thyroid cancer, is currently recruiting patients at the Weill Cornell Medical College in New York, under the supervision of Koen van Besien, MD, PhD. 1
This study (NCT0442075) represents the first time CAR T cells will be administered to humans with relapsed/refractory thyroid cancer. Based on it potential to fill an unmet medical need in the landscape, AIC100 was granted a fast track designation by the FDA for the treatment of anaplastic thyroid cancer and refractory poorly differentiated thyroid cancer in May 2021. The first patient was enrolled in October 2020.1,2
In addition to containing autologous CAR T cells, the agent expresses the transmembrane domain of CD8 alpha. AIC100 also expresses CD28 and 41BB as well as cytoplasmic signaling domain of the T cell receptor associated CD3.
The current sequential trial has an estimated enrollment of 24 patients and an estimated competition date of June 2024. The primary end point of the study is the total incidence of overall grade 3-5 adverse events (AEs) and the incidence of CAR T-related AEs. Secondary end points include detection, expansion, and persistence of AIC100 cells after infusion, the analysis of CAR T subsets by flow cytometry in peripheral blood, assessment, and analysis of CAR T-cell infiltration in tumor by biopsy at competition of treatment and/or progression, cytokine levels in plasma samples, and CAR T antibodies in peripheral blood.
In the study, 4 dose levels of AIC100 will be tested in patients with relapsed/refractory thyroid cancer. In cohort -1, patients will receive a flat dose of 1 x 106 CAR T cells. In cohort 1, they will receive a flat dose of 1 x 107 CAR T cells. In cohort 2, patients will receive a flat dose of 1 x 108 CAR T cells. In cohort 3, patients will receive a flat dos of 5 infusions of 108 CAR T cells.
Once enrolled, patients will undergo leukapheresis in order to collect autologous lymphocytes. With the exception of cohort 3, all patients will receive a single dose infusion. However, additional doses of the CAR T agent may be administered under several conditions such as stable disease or partial response per RECIST v1.1 after 30 days. Investigators deem that additional doses are in the best interest of the patients, the patient did not experience dose limiting toxicities, and there are cell doses available from the already manufactured product.1,3
Enrollment in different cohorts will be staggered so that each patient is followed for a minimum of 30 days.
In order to participate, patients must have a predefined thyroid malignancy, have measurable disease, an ECOG score of 0-2, a life expectancy greater than 8 weeks, have adequate hepatic, renal, bone marrow, and coagulation function, have recovered from prior anticancer therapy, have an absolute lymphocyte count of greater than 300mm3 prior to apheresis, and patients with reproductive potential must agree to use a highly effective method of contraception.
Patients who are breastfeeding, have uncontrolled active systemic infections, have previous treatment with an investigation gene or CAR T-cell therapy, have an active and clinically relevant central nervous system disorder such as epilepsy, evidence of another malignancy within 2 years prior to screening, are living with HIV, have an active autoimmune disease are not eligible to participate. The study also excludes patients who need long-term systemic steroids, have severe chronic disease of the kidney, liver, heart or lungs, or are allergic to any of the chemotherapy drugs given during lymphodepletion.