FDA Grants Full Approval of Afami-Cel in Synovial Sarcoma, Expands Indication to 12 and Older

The FDA has granted full approval of afamitresgene autoleucel (Tecelra; afami-cel) and expanded its indication to include pediatric patients 12 years of age and older with unresectable or metastatic synovial sarcoma. The decision converts the agent’s August 2024 accelerated approval, which had been restricted to adults, into full approval and simultaneously broadens eligible age to 12 and older, making afami-cel the first engineered T-cell therapy for a solid tumor approved for use in adolescents in the United States.¹

Patients must be HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and have tumors expressing the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices, and must have received prior chemotherapy.

Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas, and the 5-year survival rate in patients with metastatic disease is approximately 20%, with approximately one-third of patients diagnosed under the age of 30.

“For children as young as 12 with advanced synovial sarcoma, treatment options have been limited and navigating care decisions can be challenging,” Amy Armstrong, MD, associate professor of pediatrics at Washington University School of Medicine in St. Louis and director of the Solid Tumor Program at Siteman Kids at St. Louis Children's Hospital, stated in the news release.

Approval Basis: SPEARHEAD-1 Trial

The accelerated approval, granted in August of 2024, was based on results from cohort 1 of the SPEARHEAD-1 study (NCT04044768), which included 52 patients aged 16 to 75 with advanced synovial sarcoma or myxoid round cell liposarcoma.²

The full approval and expanded indication were based on results including cohorts 1, 2, and 3, across 137 patients who received a single dose of afami-cel following lymphodepleting chemotherapy, with a primary end point of overall response rate (ORR). Across all 3 cohorts, investigators reported an ORR of 43.8%, a complete response (CR) rate of 3.6%, and a median duration of response (DOR) of 5.3 months (95% CI, 4.5-8.2). Responders to the treatment had a 31.9% rate of maintained responses for 24 months or longer.¹

Pooled Analysis at ASCO Provides Further Data

A pooled analysis of phase 1 and 2 clinical trials presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting by Sandra P. D’Angelo, MD, of Memorial Sloan Kettering Cancer Center, showcased the most recent dataset for this cellular therapy.³ The pooled population comprised 153 patients who received afami-cel across the SyS Pilot Trial (NCT03132922) and SPEARHEAD-1, representing the largest dataset of patients with advanced synovial sarcoma treated with the agent. The data cutoff was December 27, 2025, with a median follow-up of 46.4 months.

In the pooled efficacy population of 153 patients, the ORR was 43.8% (95% CI, 35.8-52.0), with 7 CRs (4.6%) and 60 partial responses (39.2%). Median DOR was 7.1 months (95% CI, 4.7-10.6; range, 1.9-64.4 months), with 24-month DOR probability of 24.9% (95% CI, 14.3%-37.1%). Median time to response was 5.4 weeks (95% CI, 4.3-8.0). Median overall progression-free survival (PFS) was 4.0 months (95% CI, 3.7-5.6), with responders demonstrating substantially longer PFS than nonresponders: 9.1 months (95% CI, 6.0-13.5) vs 2.1 months (95% CI, 1.9-2.8; P <.0001).

Overall survival (OS) data from the pooled analysis underscored a pronounced response-dependent benefit. Median OS across all 153 patients was 20.2 months (95% CI, 14.6-25.7), with 12-month OS probability of 65.7% and 24-month OS probability of 41.8%. Responders, however, had a median OS of 37.5 months (95% CI, 26.3-not reached) compared with 10.9 months (95% CI, 8.5-14.1) for nonresponders (P <.0001). The ORR benefit was consistent across all prespecified subgroups, including patients with higher tumor burden (sum of lesion diameters ≥100 mm) and those with H-scores below 200, indicating lower MAGE-A4 expression.

Pediatric Outcomes

There were 7 patients aged 13 to 16 treated with afami-cel in the SPEARHEAD-1 trial.⁴ The ORR was 43% with 3 of 7 patients achieving partial responses and another 3 with stable disease. The duration of response was not reached with a median PFS of 2.8 months and OS of 18.6 months. The safety profile and pharmacokinetic profiles were comparable between the adult and pediatric populations.

Safety

In the pooled safety population, 93.5% of patients experienced at least 1 treatment-related adverse event (AE); grade 3 or higher events occurred in 41.3%.³ Cytokine release syndrome (CRS) was the most common immune-related event, affecting 73.2% of patients, with grade 3 or higher in 3.3%; 42.5% of patients with CRS required tocilizumab (Actemra) or siltuximab (Sylvant). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 4.4% of patients (all grade 1 or 2). Cytopenias were the most frequent grade 3 or higher events, with prolonged neutropenia in 14.4%, prolonged thrombocytopenia in 8.5%, and prolonged anemia in 7.8% at week 4, with median times to resolution of 7.6, 12.1, and 8.4 weeks, respectively. Two fatal treatment-emergent serious AEs were reported; one case of aplastic anemia attributed to lymphodepletion conditioning and one case of septic shock attributed to lymphodepletion.

“The availability of an engineered cell therapy for adolescents introduces an important new option for patients who are biomarker eligible, allowing us to incorporate this approach into treatment planning based on the same evidence that has guided adult care. This is a meaningful step forward for the field,” Armstrong stated in the news release.¹

REFERENCES

1. US WorldMeds® Receives Full U.S. FDA Approval of TECELRA® (afamitresgene autoleucel) with an Expanded Indication, Extending the First Approved Engineered T-Cell Therapy for a Solid Tumor to Children as Young as 12. News release. US World Meds. June 22, 2026. Accessed June 23, 2026. https://tinyurl.com/yrm9vurr

2. 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

3. D’Angelo SP, Araujo DM, Razak A, et al. Pooled analyses of clinical outcomes with afamitresgene autoleucel (afami-cel) in metastatic synovial sarcoma. J Clin Oncol. 2026;44(suppl 16):11505. doi:10.1200/JCO.2026.44.16_suppl.11505

4. Armstrong AE, Minard-Colin V, Glod J, et al. Efficacy and safety of engineered TCR-T cell therapy (afami-cel, lete-cel) in pediatric synovial sarcoma. J Clin Oncol. 2026;44(suppl 16):11569. doi:10.1200/JCO.2026.44.16_suppl.11569