Engineered Cell Therapy Receives FDA Approval for Solid Tumors for the First Time

On August 2, 2024, the FDA (United States Food and Drug Administration) granted accelerated approval to afamitresgene autoleucel (afami-cel) (Tecelra, Adaptimmune LLC) for the treatment of advanced synovial sarcoma.

A Groundbreaking Treatment Approval for Solid Tumors

Tecelra is the first engineered cell therapy for solid tumors. It is specifically suitable for adults with unresectable or metastatic synovial sarcoma who have previously received chemotherapy, are positive for various human leukocyte antigens (HLA), and whose tumors express melanoma-associated antigen A4 (MAGE-A4).

A solid tumor is a type of cancer that develops in body tissues or organs, does not originate in the blood or bone marrow, and grows as a mass.

Synovial sarcoma is a rare type of cancer that develops in soft tissues, usually near joints. This tumor originates in synovial tissues and occurs particularly in young adults.

A Targeted Cellular Immunotherapy Approach

This single-dose cellular therapy targets the MAGE-A4 protein, which is highly expressed in synovial sarcoma.

Synovial sarcoma is a rare cancer that affects approximately 1000 people each year in the United States. Cancer cells form tumors in soft tissues, usually in the limbs.

Adults with metastatic synovial sarcoma often face limited treatment options as well as the risk of cancer spread or recurrence. This approval is an important milestone in the development of an innovative, safe, and effective treatment for this rare but potentially fatal disease.

Similarities to and Differences from CAR T-Cell Therapy

Like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, T-cell receptor therapy involves modifying patients' T cells to fight cancer. While CAR-T therapy adds an artificial receptor to target a specific protein on the surface of cancer cells, T-cell receptor therapy modifies existing receptors to recognize a range of antigens on the surface of cancer cells—a promising strategy for targeting solid tumors.

Accelerated Approval of Tecelra: Results of the SPEARHEAD-1 Phase 2 Trial

Accelerated approval of Tecelra was based on the SPEARHEAD-1 phase 2 trial, in which 44 patients with synovial sarcoma received a single infusion. The trial enrolled 52 patients, but eight did not receive Tecelra, three died, and one withdrew.

According to the FDA announcement, the overall response rate was 43.2%, and the median response time was 4.9 weeks. The median duration of response was recorded as 6 months (95% CI, 4.6 months to not estimable). Among responders, 39% had a response duration of 12 months or longer.

These results suggest that a one-time treatment with Tecelra has the potential to extend life while allowing responders to stop chemotherapy.

The prescribing information includes a boxed warning for serious or life-threatening cytokine release syndrome.

The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, are cytokine release syndrome, nausea, vomiting, fatigue, infections, fever, constipation, shortness of breath, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, are decreased lymphocyte count, neutrophil count, white blood cell count, red blood cell count, and platelet count.

The recommended dose ranges from 2.68x10⁹ to 10x10⁹ MAGE-A4 T-cell receptor–positive T cells. The FDA announcement recommends not using a leukodepleting filter or prophylactic systemic corticosteroids.

According to Fierce Pharma, the list price of the one-time treatment is 727,000 dollars.