Afamitresgene autoleucel is a genetically modified autologous T cell immunotherapy consisting of CD4 and CD8 positive T cells transduced with a self-inactivating LV to express an affinity-enhanced TCR specific for human MAGE-A4 on the cell surface.
The TCR recognizes an HLA-A*02 restricted MAGE-A4 peptide. MAGE-A4 is an intracellular cancer-testis antigen that has restricted expression in normal tissues and is expressed in synovial sarcoma. Antigen-specific activation of afamitresgene autoleucel via TCR-peptide-HLA-A*02 complex results in T cell proliferation, cytokine secretion, and killing of MAGE-A4/HLA-A*02 expressing synovial sarcoma cells.
In patients with synovial sarcoma who were treated with afamitresgene autoleucel, serum concentrations of cytokines and other soluble factors involved in cellular homeostasis, T cell activation, and inflammation (e.g. IFNγ, IL-6, IL-8, IL-15, and IL-2Rα) increased post-infusion, peaking between Days 3-8.
Afamitresgene autoleucel exhibited an initial engraftment and expansion phase followed by contraction, and then persistence. High inter-individual variability was observed.
The pharmacokinetics of afamitresgene autoleucel in patients with synovial sarcoma are summarized in the following table.
Pharmacokinetics of Afamitresgene Autoleucel in SPEARHEAD-1 (Cohort 1)*:
| PK Parameter | N | Statistics | Value |
|---|---|---|---|
| tmax (day) | 44 | Median (range) | 7 (1-89) |
| Cmax (DNA copies/μg) | 44 | Geometric mean (CV%) | 189269 (109.1%) |
| AUC0-7D (day*DNA copies/μg) | 44 | Geometric mean (CV%) | 729653 (110.8%) |
| AUC0-28D (day*DNA copies/μg) | 41 | Geometric mean (CV%) | 3074205 (164.7%) |
| AUC0-3M (day*DNA copies/μg) | 35 | Geometric mean (CV%) | 4988965 (242.7%) |
| AUC0-6M (day*DNA copies/μg) | 33 | Geometric mean (CV%) | 6784047 (313.4%) |
* All patients received a dose within the range of 2.68 x 109 to 10 x 109 MAGE-A4 TCR positive T cells.
The pharmacokinetics of afamitresgene autoleucel (Cmax, AUC0-7D, AUC0-28D, AUC0-3M, AUC0-6M) were not impacted by body weight, body mass index, sex, age (range: 19 to 76 years), and baseline tumor sum of longest diameter (SLD).
Hepatic and renal impairment studies of afamitresgene autoleucel were not conducted.
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