Dr Ku on the Rationale for Evaluating JNJ-90014496 in Relapsed/Refractory LBCL

“We know that CD19-directed CAR T-cell therapies have revolutionized the way we treat patients with relapsed/refractory LBCL. However, despite this effective T-cell therapy, most patients don’t achieve long-term remissions. We know that relapses can occur due to a variety of reasons, and one of those is antigen escape, where the lymphoma cells lose the target antigen on the cell membrane.”

Matthew Ku, MBBS, FRACP, RACP, FRCPA/RCPA, PhD, an associate professor and the lymphoma stream lead at St Vincent’s Hospital, detailed the rationale for evaluating JNJ-90014496 for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) in a global phase 1b study (NCT05421663).

CD19-directed CAR T-cell therapies have significantly affected the treatment paradigm for patients with relapsed/refractory LBCL, Ku began. However, although these CAR T-cell therapies have been shown to be effective, many patients are unable to achieve long-term remissions following this treatment, he explained. This gap could be attributed to many reasons, including antigen escape, in which the lymphoma cells lose the target antigen on the surface of the cell, according to Ku. Nevertheless, the novel dual CD19/CD20-directed bispecific CAR T-cell therapy JNJ-90014496 could target validated antigens to ultimately avoid antigen escape seen with current CD19-directed CAR T-cell therapies, which could improve upon the efficacy seen with previously developed agents, Ku emphasized.

Patients enrolled on the study were at least 18 years of age with relapsed/refractory LBCL and had received 2 or more prior lines of therapy if they were transplant eligible or 1 prior line of therapy if they were transplant ineligible, Ku continued. Following enrollment, patients received apheresis, he said. Similar to other CAR T-cell therapies, he explained that JNJ-90014496 is an autologous treatment. Once the treatment is subsequently manufactured to have CD19/CD20 receptors, it is reinfused into patients, he said. Of note, the initial dose was 2 million CAR-positive T cells per kg, he noted. Once this dose was determined to be safe, patients were treated with 2 more doses. Specifically, 1 dose was a fixed dose of 150 million CAR-positive T cells, and the other was a dose of 75 million CAR-positive T cells, which was established to be the recommended phase 2 dose, as it was the most efficacious and safe of the 3 doses, Ku concluded.