In an open-label,
nonrandomized phase II trial, D'Angelo et al. (2024) studied
afamitresgene autoleucel (
afami-cel) in HLA-A*02–positive populations aged
16 to 75 years, with advanced (i.e., metastatic or unresectable) synovial sarcoma
or myxoid round cell lipsarcoma. Although synovial sarcoma and myxoid round cell
liposarcoma are two distinct diseases, they both express melanoma-associated
antigen A4 (MAGE-A4). All individuals received at least two previous lines of
therapy and were followed up to a median of 32.6 months. Of 373 individuals
prescreened for HLA eligibility (e.g., HLA-A*02:01, -A*02:02, -A*02:03, -A*02:06) and MAGE-A4 expression, 52 were in the
modified intention-to-treat (mITT) population who subsequently underwent
leukapheresis and treatment. Although the HLA-A*02 alleles produce varying proteins, they all have the same protein sequence as those in the peptide-binding domain, and were therefore deemed eligible for study inclusion. Individuals positive for the HLA-A*02:05 allele were excluded due to potential alloreactivity previously demonstrated in a preclinical trial.
The primary endpoint
of overall response rate—defined as a complete or partial response based on the Response Evaluation Criteria in Solid Tumors v1.1 (RECIST)—was reached by 37% (19 of 52) of the mITT group (95% confidence interval [CI], 24–51). The
best overall response of all 19 individuals was partial response (PR), where at least a 30% decrease in the sum of diameters of target lesions occurred
from baseline. Median time to a confirmed response was 4.9 weeks (95% CI, 4.3–8.1) with a median response duration of 11.6 months (95% CI, 4.4–18). Seventeen of 19 were those with synovial sarcoma. Median overall and progression-free survival of 31 individuals analyzed was 15.4 months (95% CI, 10.9–28.7) and 3.7 months (95% CI, 2.8–5.6), respectively; however, median overall survival in synovial sarcoma individuals with a RECIST partial response could not be determined given censored data, where censorship occurred due to the individual being alive, losing to follow-up, or undocumented progression to death. The estimated overall survival probability in this population was 90% at 12 months and 70% at 24 months. Cytokine release syndrome occurred in 71% of 52 individuals, comparable results to that of other immunotherapies.
A tumor response from 37% of participants met the primary endpoint of at least 18%, an overall response rate typically seen in similar populations undergoing alternative second-line chemotherapies. Among those with synovial sarcoma who responded to afamitresgene autoleucel (afami-cel), the therapy demonstrated a reduction in the size of target lesions by at least 30% of their initial diameter and may be associated with increased length of survival. Thus, the evidence for afamitresgene autoleucel (Tecelra) is sufficient for providing a meaningful net health outcome in individuals with advanced synovial sarcoma.
