Fatal Adverse Event Halts Enrollment in Atara Mesothelioma Trial

Patient enrollment for the clinical trial, which was testing Atara’s autologous chimeric antigen receptor (CAR) T-cell immunology therapy called ATA2271, has been paused.

Atara Biotherapeutics, an immunology-focused biopharmaceutical company based in San Francisco, announced a fatal serious adverse event (SAE) with a patient in a clinical trial at Memorial Sloan Kettering Cancer Center (MSK).

New Patient enrollment in the clinical trial, which is testing Atara’s autologous chimeric antigen receptor (CAR) T-cell immunology therapy called ATA2271, has been paused - an action the Food and Drug Administration supported - while Atara, MSK and the FDA review the case.

“The safety of every patient participating in studies we are funding or conducting is of the utmost priority for Atara. Clinical evaluation of the case remains ongoing, and we are working closely with investigators at MSK, who are conducting the ATA2271 study under their IND, 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,” said Jakob Dupont, M.D., head of global research and development at Atara.

Atara’s ATA2271 therapy is the latest in the company’s line of immunotherapy treatments designed to treat patients with cancer and autoimmune diseases. ATA2271 is an autologous, second-generation immunotherapy treatment that uses T-cells, a type of immune cell, to target mesothelin. Mesothelin is a type of protein called an antigen, and when it is overexpressed, it frequently leads to cancer, particularly mesothelioma and other solid tumors.

In this clinical trial, Atara worked with MSK to recruit patients who were suffering from malignant pleural mesothelioma, a cancer commonly caused by mesothelin anomalies. Normally, patients with malignant pleural mesothelioma only survive for about 9-17 months, even with aggressive chemotherapy and radiation treatments. Atara hopes the ATA2217 CAR T-cell treatment can help harness the body’s natural immune system to fight the tumor without harming other body systems.

Phase I of the clinical trial went well, and the therapy was found to be well tolerated. In January 2022, Atara announced positive results. In both in vitro and in vivo functional studies, the therapy effectively suppressed tumor growth and increased cell function in the presence of suppressive checkpoint ligands commonly associated with solid tumor microenvironments.

The previous clinical success of ATA2217 further complicates the fatal serious adverse event in the ongoing trial. MSK and Atara noted that the patient had “a history of multiple malignancies and other comorbidities” during treatment for advanced recurrent mesothelioma. MSK and the FDA are investigating what happened to the patient. Part of the investigation will assess whether ATA2217 was responsible for the death, and if so, to what extent.

Although the clinical trial for ATA2217 has been paused, Atara emphasized that other clinical work for lifesaving treatments will continue. Currently, Atara is filing for an Investigational New Drug (IND) for its ATA3271 immunotherapy, a separate, off-the-shelf, allogeneic CAR-T therapy that is also designed to treat mesothelioma and similar tumors. Atara will continue with its application to the FDA. Atara’s treatments ATA3271, ATA3219, tab-cel and ATA188 will all continue, as they are all based on the same T-cell platform and have had high safety and tolerability results in over 400 patients.

Atara will also continue its research in other areas of immunotherapy. Using its novel allogeneic Epstein-Barr virus (EBV) T-cell platform, the company will continue working on cures for cancers and immune diseases such as multiple sclerosis and hematologic malignancies.