FDA Approves Afamitresgene Autoleucel for Certain Unresectable or Metastatic Synovial Sarcoma

On August 2, 2024, the US Food and Drug Administration (FDA) granted accelerated approval to afamitresgene autoleucel for the treatment of adult patients with unresectable or metastatic synovial sarcoma who had received prior chemotherapy and 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 an FDA-approved or -cleared companion diagnostic device. Afamitresgene autoleucel represents the first engineered cell therapy for a solid tumor to be approved in the US.

Continued approval for this treatment in this indication may rely upon verification and description of clinical benefit from a confirmatory trial. This accelerated approval decision was made based upon overall response rate and duration of response data from cohort 1 of the SPEARHEAD-1 trial.

Cohort 1 was the main investigational cohort of this international, open-label, phase 2 trial. There were 44 patients with HLA-A*02 and metastatic or unresectable synovial sarcoma or myxoid round cell liposarcoma expressing MAGE-A4 in this cohort who completed treatment. All patients had received ≥1 previous line of anthracycline-containing or ifosafamide-containing chemotherapy. In this trial, patients received a single dose of afamitresgene autoleucel following lymphodepletion. The primary end point of this trial was overall response rate (ORR) in cohort 1. A supporting efficacy outcome was duration of response (DOR).

The ORR as evaluated by independent review was 43.2%. The median time to response was 4.9 weeks and the median DOR was 6 months. Of the patients who responded to treatment, 45.6% had a response ≥6 months, and 39.0% had a response ≥12 months.

There is a Boxed Warning on afamitresgene autoleucel for serious or fatal cytokine release syndrome (CRS) which may be severe or life-threatening.

The most common non-laboratory adverse events occurring in ≥ 20% of patients were cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema.

The recommended dose of afamitresgene autoleucel is between 2.68 x 109 and 10 x 109 MAGE-A4 T cell receptor positive T cells, administered in one or more infusion bags. There should not be a leukodepleting filter or prophylactic systemic corticosteroids used.

Sources:

FDA grants accelerated approval to afamitresgene autoleucel for unresectable or metastatic synovial sarcoma. Accessed on Aug 2, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-afamitresgene-autoleucel-unresectable-or-metastatic-synovial-sarcoma

D’Angelo SP, Araujo DM, Abdul Razak AR, et al. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): An international, open-label, phase 2 trial. Lancet. 2024;403(10435):1460-1471. doi:10.1016/S0140-6736(24)00319-2