FDA Grants Full Approval to Afami-Cel for Advanced Synovial Sarcoma

The FDA has granted full approval of afamitresgene autoleucel (afami-cel; Tecelra) for the treatment of adult patients and pediatric patients 12 years of age and older 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.¹

The approval builds on the August 2024 accelerated approval of afami-cel, when it was initially indicated only for adult patients.²

Regular approval was supported by data from the cohorts 1, 2, and 3 of the SPEARHEAD-1 trial (NCT04044768), which demonstrated that treatment with afami-cel led to an overall response rate (ORR) of 43.8%, including a complete response rate of 3.6%.¹ The median duration of response (DOR) was 5.3 months (95% CI, 4.5-8.2), and 31.9% of responders achieved a duration of response of at least 24 months.

"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, an 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 a news release. "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."

What was the design of the SPEARHEAD-1 trial?

The single-arm, open-label trial enrolled patients 10 to 75 years of age with cytogenetically confirmed advanced synovial sarcoma (cohorts 1, 2, and 3) or myxoid liposarcoma/myxoid round cell liposarcoma (cohort 1).³ Prior treatment with an anthracycline- or ifosfamide-containing regimen was required. Other key inclusion criteria comprised measurable disease per RECIST 1.1 criteria prior to lymphodepletion, HLA-A*02:01–, HLA-A*02:02–, HLA-A*02:03–, or HLA-A*02:06–positive tumors; and positive MAGE-A4 expression confirmed by central laboratory. An ECOG performance status of 0 or 1 was also required (Lansky performance status of ≥60% for those 16 years of age and younger).

Following lymphodepletion, patients received a single infusion of afami-cel at 1.0 x 10⁹ to 10 x 10⁹ cells.

ORR served as the trial’s primary end point. Key secondary end points included safety, best response in cohort 1, time to response, DOR, progression-free survival, and overall survival.

What is the safety profile of afami-cel?

Previously reported data from cohort 1 of SPEARHEAD-1 showed that the most common adverse effects (AEs) of any grade reported in at least 20% of patients included cytokine release syndrome (CRS), nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema.

Grade 3/4 laboratory abnormalities reported in at least 20% of patients comprised decreased lymphocyte count, decreased neutrophil count, decreased white cell blood count, decreased red blood cell, and decreased platelet count.

CRS and pleural effusion were the most common serious AEs reported in at least 5% of patients.

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 WorldMeds. June 22, 2026. Accessed June 22, 2026. https://www.prnewswire.com/news-releases/us-worldmeds-receives-full-us-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-12-302806599.html?tc=eml_cleartime
2. Adaptimmune receives U.S. FDA accelerated approval of Tecelra (afamitresgene autoleucel), the first approved engineered cell therapy for a solid tumor. News release. Adaptimmune Therapeutics. August 1, 2024. Accessed June 22, 2026. https://www.adaptimmune.com/investors-and-media/news-center/press-releases/detail/271/adaptimmune-receives-u-s-fda-accelerated-approval-of
3. Spearhead 1 study in subjects with advanced synovial sarcoma or myxoid/​round cell liposarcoma. ClinicalTrials.gov. Updated February 2, 2026. Accessed June 22, 2026. https://clinicaltrials.gov/study/NCT04044768
4. Tecelra. Prescribing information. Updated January 2026. Accessed June 22, 2026. https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2ddd66e1-8036-4a4e-babe-4d673e660bf5#section-6.1