Early results from a Phase I clinical trial of AT101, a novel CAR T-cell therapy, indicate a 100% complete response rate at the higher dose levels studied. The therapy utilizes a distinct binding mechanism to target CD19, according to researchers from the Perelman School of Medicine and Penn Medicine’s Abramson Cancer Center.
The findings, published in Molecular Cancer and presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, offer a promising new approach for patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL).
Targeting CD19 with a Novel Epitope
Existing CD19 CAR T-cell therapies target the same epitope, and some patients do not respond or eventually relapse. To address this, Marco Ruella, assistant professor of hematology-oncology and scientific director of the Lymphoma Program, along with AbClon Inc, co-developed AT101. This therapy uses cells from the same patient but targets a different CD19 epitope closer to the cell membrane via a novel antibody.
The Phase I trial, conducted in South Korea, enrolled 12 patients with relapsed or refractory B-cell NHL.
Implications for CAR T-cell Therapy
"We’ve learned that the way you design your CAR really matters. Designing a different CAR might drastically change the way the T cells work, potentially allowing that CAR T cell product to work where other CAR T cell products have failed," Ruella said. "We were not expecting such a drastic early difference in this study. The CART19 products that are already FDA-approved are very effective, and it’s not easy to do better. While there is not a randomized trial of this product yet, the initial results seem very promising, and we look forward to moving into the planned Phase II portion of the study."
The early data suggests that AT101 could provide a valuable alternative for patients who have exhausted other treatment options. Further studies are needed to confirm these findings and assess the long-term efficacy and safety of AT101.
