FDA clears Adaptimmune T-cell therapy for soft tissue cancer

The FDA has given accelerated approval to a groundbreaking T cell-based therapy from Adaptimmune for synovial sarcoma, becoming the first new treatment for the rare soft tissue cancer in more than a decade.

Tecelra (afamitresgene autoleucel) has also become the first FDA-approved, engineered T-cell therapy for solid tumours, and is indicated for adults with unresectable or metastatic synovial sarcoma when other prior chemotherapy does not work, according to the Anglo-American biotech. It is based on the patient's own cells and is delivered as a one-time infusion.

Synovial sarcomas arise in muscle and connective tissue and account for approximately 5% to 10% of all soft tissue sarcomas in the US, of which there are approximately 13,400 new cases each year, mainly in younger adults aged under 30.

They tend to be slow-growing but can spread to other parts of the body easily, and the five-year survival rate for patients diagnosed at an advanced stage can be as low as 20%.

Tecelra – which targets the MAGE-A4 antigen on tumour cells, can only be used in patients who have been tested to see if the therapy is suitable, a process that involves HLA testing for compatibility with the treatment. A check that the sarcoma is MAGE-A4-positive is also needed, using a companion diagnostic developed by Agilent.

In the pivotal SPEARHEAD-1 trial published in The Lancet earlier this year, afami-cel demonstrated an objective response rate (ORR) of around 39% among heavily pre-treated patients with advanced synovial sarcoma, along with a 17-month median overall survival (OS) that Adaptimmune said represented a significant advance in treatment for this patient population. Typically, ORRs for second-line synovial sarcoma therapies have ranged between 14% and 18%.

Adaptimmune's chief executive Adrian Rawcliffe said the FDA approval is a "momentous step" for the company's efforts to redefine the treatment of cancer and the culmination of "a decade of groundbreaking R&D." The company is holding a conference call later today to brief analysts and investors on the next stages of the rollout.

Next up for Adaptimmune is a filing next year for a second T-cell therapy, NY-ESO-1-targetting letetresgene autoleucel or lete-cel, for synovial sarcoma and myxoid/round cell liposarcoma (MRCLS). Adaptimmune has previously modelled peak sales of around $400 million a year for the franchise, despite the rarity of the sarcomas they target.

Another company developing a T-cell therapy for solid tumours is Immatics, whose MAGE-A4 and MAGE-A8-directed IMA401 candidate – partnered with Bristol-Myers Squibb – is in a phase 1 basket trial in various solid tumour types including sarcomas.