Adaptimmune Confident T-Cell Therapy Will Hit Efficacy Endpoint

Adaptimmune Therapeutics is poised to file a Biologics License Application (BLA) in 2022 after announcing that its ongoing Phase II study on the effectiveness of T-cell therapy afami-cel to treat cancer will meet its primary endpoint by the end of this year. 

Reporting at the Connective Tissue Oncology Society annual meeting, the company said that afamitresgene autoleucel (afami-cel), formerly called ADP-A2M4, had a significantly positive effect on patients diagnosed with myxoid/round cell liposarcoma (MRCLS) and advanced synovial sarcoma. 

Its pivotal Phase II SPEARHEAD-1 trial tested the drug on 50 patients aged 19 to 73 years and had received one to 12 lines of therapy prior (median three). The doses ranged from 2.7 to 10 billion transduced SPEAR T-cells, with a median of 8.5 billion. 

The primary endpoint, which is response according to RECIST v1.1, will be evaluated via an Independent Review. Based on the overall response rate from current results, Adaptimmune said it is confident of hitting this endpoint during the final analysis scheduled before the year ends, using a one-sided exact-based Clopper-Person 97.5% confidence interval. If the lower bound of the CI is higher than the historical second line therapies, which is at 18%, then the trial will have met its efficacy threshold. 

So far, the Independent Review reveals the overall response rate to be at 34%, covering 36% of patients with synovial sarcoma and 25% of patients with MRCLS. The disease control rate is 85%, while 75% of the participants demonstrated an ongoing response for up to 65.3 weeks post-infusion. Some adverse events were observed in 66% of the patients, though most were of low grade, leading the company to call it well-tolerated and as having a favorable benefit:risk profile. 

Translational findings also confirm that afami-cel is active against MAGE-A4 expressing targets both in vivo and in vitro. MAGE-A4 is highly expressed in both diseases. The cutoff for these data is September 1, 2021. 

"Afami-cel would provide a new treatment option for patients with synovial sarcoma, offering benefits that we have rarely seen with therapies currently available for this patient population. This is a game-changer for patients with a high unmet medical need," said Dr. Brian A. Van Tine, a Professor of Medicine and of Pediatrics at the Washington University School of Medicine in St. Louis. 

Adaptimmune intends to treat around 90 patients with its new drug in two cohorts. Enrollment for Cohort 1 is done, while Cohort 2 is still recruiting participants. The results from Cohort 1 will be used to support the company's BLA filing next year.