Enrollment Pauses in Mesothelioma CAR T-Cell Therapy Trial
The pause follows a fatal serious adverse event in the first patient treated in the highest dose cohort.
Atara Biotherapeutics and Memorial Sloan Kettering (MSK) have paused enrollment in their phase 1, chimeric antigen receptor (CAR) T-cell therapy trial (NCT04577326) following a fatal, serious adverse event (AE).1
The therapy in question is ATA2271, a next-generation, autologous, mesothelin-targeted investigational therapy for the potential treatment of malignant pleural mesothelioma. MSK, the trial site, voluntarily paused enrollment in the trial after the death pending more information and the FDA has notified MSK of itsagreement with this move.
“The safety of every patient participating in studies we are funding or conducting is of the utmost priority for Atara,” Jakob Dupont, MD, head, global research & development, Atara, said in a statement.1 “Clinical evaluation of the case remains ongoing, and we are working closely with investigators at MSK, who are conducting the ATA2271 study under their [investigational new drug application], to establish the underlying causes of the event. We anticipate providing a further update in the coming weeks following further discussion and consultation with MSK.”
The patient that died was undergoing treatment for advanced recurrent mesothelioma and had a history of multiple malignancies and other comorbidities. MSK is evaluating the death and the extent of its relationship to ATA2271 treatment.
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The trial has so far enrolled 6 patients in the 2 lowest dose cohorts of 1x106 cells/kg and 3x106 cells/kg of intrapleural ATA2271. Investigators have observed no dose-limiting toxicities in these patients to this point. The patient that died was the first patient to be dosed in the higher dose cohort of 6x106 cells/kg.
Atara remains hopeful that its therapy may be able to improve upon the median survival of treated patients with malignant pleural mesothelioma, which ranges from 9-17 months with successful completion of chemotherapy, aggressive surgical resection, and radiation therapy.
The company is continuing to advance their investigational new drug application-enabling studies for their allogeneic CAR T-cell therapy, ATA3271, also for the potential treatment of advanced mesothelioma. ATA3271 uses next-generation PD1DNR and 1XX CAR technologies as well as Atara’s allogeneic Epstein-Barr virus (EBV) T-cell platform, which is also used to develop itsEBV-targeting, investigational cell therapy candidate ATA188 for the potential treatment of multiple sclerosis (MS).
Atara’s approach to treating MS has been further validated by recent studies that have elucidated the link between EBV and MS.2,3 CGTLive previously spoke with Dupont about the body of research that has led to these publications and ATA188’s promise in treating MS. Watch the interview below.
