FDA clears IND application for CAR T-cell therapy for advanced mesothelioma
The FDA cleared an investigational new drug application for ATA2271, a chimeric antigen receptor T-cell therapy for the treatment of advanced mesothelioma, according to the agent’s manufacturer.
ATA2271 (Atara Biotherapeutics) is an autologous CAR T-cell therapy that targets the mesothelin antigen expressed on the surface of certain solid tumors.
The investigational agent — being developed as part of a collaboration with Memorial Sloan Kettering Cancer Center — combines two novel proprietary technologies, according to Atara.
The first is a 1XX costimulatory domain technology to simultaneously extend T-cell effector function while limiting cell exhaustion. This technology was developed by the lab of Michel Sadelain, MD, PhD, director of the Center for Cell Engineering at Memorial Sloan Kettering.
The second is a genetic modification to the CAR T cells to achieve checkpoint blockade by PD-1 DNR that overcomes the immune suppression of PD-L1. The technology was developed in collaboration with Prasad S. Adusumilli, MD, FACS, a thoracic surgeon who specializes in solid tumor cellular therapies and codirector of the mesothelioma program at Memorial Sloan Kettering.
“This milestone marks an important moment in the advancement of cell and gene immunotherapy for patients, for the field and for Atara,” Jakob Dupont, MD, global head of research and development at Atara Biotherapeutics, said in a company-issued press release. “As the first-ever CAR T therapy leveraging the combination of PD-1 DNR checkpoint inhibition and 1XX CAR signaling technologies to enter the clinic, we are advancing a unique CAR T program with the goal of developing transformative therapies for patients with solid tumors.”
The FDA’s IND clearance was based on preclinical research presented by Adusumilli’s lab at this year’s American Association for Cancer Research Virtual Annual Meeting II.
The studies showed that ATA2271 was associated with less cell exhaustion, improved functional persistence, serial cell killing and enhanced in vivo efficacy compared with previous-generation, mesothelin-directed CAR T-cell therapy.
The IND clearance allows Atara to initiate an open-label, single-arm, phase 1 clinical trial of ATA2271 for patients with advanced mesothelioma.
The study’s principal investigator will be Roisin E. O'Cearbhaill, MD, a medical oncologist and research director of the Gynecologic Medical Oncology Service at Memorial Sloan Kettering.