CAR-T and other cell therapies have seen success in blood cancers but have shown limited effect in solid tumors. Adaptimmune aims to change that with an engineered T-cell receptor approach, and its first phase 2 data, from patients with rare soft-tissue sarcomas, look promising.
The data come from 33 evaluated patients in a study that will eventually test the cell therapy in a total of 45 patients. Of those, 29 had synovial sarcoma, a cancer of the soft tissue that can be found in various parts of the body, and four had myxoid/round cell liposarcoma, a type of cancer that occurs in fat cells. All of the patients had tried at least three other lines of therapy.
The MAGE-A4-targeting treatment, afamitresgene autolecel, shrank tumors in 39.3% of the patients. It did better in the patients with synovial sarcoma, shrinking tumors in 41.4% of them, and curbing tumor growth in 86.2%. Two of the 29 patients, or 7%, saw their tumors completely cleared.
The treatment, once known as ADP-A2M4 and called afami-cel for short, shrank tumors in 25% patients with myxoid/round cell liposarcoma, with the caveat that this figure comes from a very small group of just four patients.
The results, to be presented virtually at the annual meeting of the American Society of Clinical Oncology next month, will form the basis of an FDA filing for afami-cel next year. If approved, it would become a new option for patients who, despite undergoing treatments like surgery, radiation and chemotherapy, more often than not die from their cancer.
“The therapeutic options for patients with synovial sarcoma or myxoid/round cell liposarcoma are very limited. If they’re not essentially cured from a surgical approach, most of the patients, the vast majority, die from their disease,” said Elliot Norry, M.D., chief scientific officer of Adaptimmune.
“The first line of treatment for them is a chemotherapy regimen. A good number of patients respond to that, but it doesn’t cure them, so you end up having relapsed disease,” Norry said, adding that the few second-line medicines that are used work for very few patients and subject them to ongoing side effects.
“The response rate we are seeing in this population of give or take 40% represents a massive difference in response as compared to currently available second-line options. It’s not even in the same sort of ballpark, from around 10% and the low teens to the 40% range,” Norry said.
The results could get even better as more patients are dosed and followed over time, said Norry and Adrian Rawcliffe, CEO of Adaptimmune.
About 60% of the patients suffered cytokine release syndrome, a well-known side effect of cell therapy where the engineered T cells work too well and activate the immune system too strongly. But most of those cases, 95%, were mild to moderate.
“Cytokine release syndrome is expected, so from our standpoint, we haven’t tried to avoid it and have tried to learn how to manage it. We accept it is part of the successful treatment of a tumor with T-cell therapies,” Norry said.
Other side effects were blood-related and tolerable or reversible, including a low white blood cell count, nausea, anemia and fatigue.
Adaptimmune is developing TCR-T therapies based on its SPEAR (specific peptide enhanced affinity receptor) T-cell platform, which allows the company to engineer T cells to target and destroy multiple types of solid tumors. It hopes to bring forth treatments for multiple solid tumors, including liver, lung and head and neck cancers, but synovial sarcoma was a natural first target for afami-cel.
“Several tumors express MAGE-A4 as a target and probably the most prevalent expression is in synovial sarcoma... In a way, the indication chose us as much as we chose it,” Norry said.
It may not be the biggest indication, but it’s a good launchpad for a company that needs to build its “manufacturing and commercial muscle” ahead of its first approval.
Besides filing a BLA for afami-cel based on the first 45 patients in this trial, Adaptimmune will enroll another 45 patients in a second cohort to better understand the treatment’s safety profile and figure out which patients benefit from it the most, Rawcliffe said.
It is also working on a second-generation program, a TCR-T cell treatment targeting MAGE-A4 and CD8, for lung, esophageal, head and neck and bladder cancers, with plans to unveil data at the European Society for Medical Oncology meeting in the fall.