Researchers from the University of Pennsylvania’s Abramson Cancer Center presented preliminary results of an ongoing Phase I clinical trial demonstrating successful re-treatment with CAR T cell therapy for patients whose cancers relapsed after previous CAR T therapy at the 2022 American Society of Hematology (ASH) Annual Meeting (Abstract 2016).
CAR T therapies have revolutionized blood cancer treatment over the last decade, providing hope for patients who have run out of conventional treatment options, but patients whose cancers return or stop responding to CAR T therapy have limited options for further treatment.
The first-in-human study (NCT04684563) evaluated a novel fourth-generation CAR T therapy in patients with non-Hodgkin lymphoma (NHL) who had previously received CAR T therapy that failed to stop their cancer. The study is the first clinical trial in the United States with anti-CD19 CAR T cells secreting interleukin 18 (IL 18).
The early results show this combination approach is safe and did not result in new or increased side effects compared to other commercially available CAR T therapies.
Senior author and CAR T pioneer Carl June, MD, led the preclinical research that demonstrated IL18 could enhance CAR T activity. “We designed an ‘armored’ CAR that secretes IL18 and tested it in mice, where we found it to have potent antitumor efficacy in our preclinical studies,” said June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center.
Among the first seven patients who received huCART19-IL18 – including those who previously did not respond to or relapsed following treatment with commercial CAR T cell therapies – all responded to the therapy (four patients had a complete response and three patients had a partial response). None of the four patients whose cancers completely responded to treatment at month three have seen their disease return, and all patients are alive at a median follow-up of eight months.
“Patients whose cancers don’t respond or become refractory to CAR T therapy tend to have poor outcomes, so we are very motivated to find new options for them. Although these are preliminary results, it’s encouraging to see how well these patients have done. Our team at Penn is very excited about this ongoing project and these early results continue to motivate us.”
Jakub Svoboda, MD, lead author, associate professor of Hematology-Oncology at Penn