On August 2, 2024, the FDA granted accelerated approval to afamitresgene autoleucel (Tecelra; Adaptimmune, LLC), a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T-cell immunotherapy, for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive, and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or -cleared companion diagnostic devices.
Efficacy was evaluated in SPEARHEAD-1, cohort 1, a multicenter, single-arm, open-label clinical trial that enrolled HLA-A*02:01-03 and -06 allele-positive patients with inoperable or metastatic synovial sarcoma who had received prior systemic therapy with either doxorubicin and/or ifosfamide and whose tumor expressed the MAGE-A4 tumor antigen. Patients received lymphodepleting chemotherapy with fludarabine and cyclophosphamide.
Fifty-two patients with synovial sarcoma were enrolled and underwent leukapheresis, 8 of whom did not receive afamitresgene autoleucel due to death (n=3), loss of eligibility prior to lymphodepleting chemotherapy (n=3), withdrawal by patient (n=1), and investigator decision (n=1). Forty-five patients received lymphodepletion and 1 patient withdrew consent before treatment, for a total of 44 patients who received a single infusion of afamitresgene autoleucel.
The main efficacy outcome measure was ORR according to RECIST v1.1 evaluated by independent review, supported by DOR. ORR was 43.2% (95% CI, 28.4-59.0). The median time to response was 4.9 weeks (95% CI, 4.4-8). The median DOR was 6 months (95% CI, 4.6-not reached). Among patients who were responsive to the treatment, 45.6% and 39.0% had a DOR ≥6 months and 12 months, respectively.
The prescribing information includes a Boxed Warning for serious or fatal cytokine release syndrome (CRS), which may be severe or life-threatening.
The most common nonlaboratory adverse reactions (≥20%) were CRS, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, noncardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities (≥ 20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased.1
Editor’s note: This report was based on statements issued by the FDA and pharmaceutical companies mentioned in the approvals.
References
- Food and Drug Administration. FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma. August 2, 2024. Accessed August 20, 2024. www.fda.gov/drugs/resources-information-approveddrugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-ormetastatic-synovial-sarcoma