JNJ’4496 Demonstrates Clinical Benefit, Safety in Relapsed/Refractory LBCL

“These findings support further development of JNJ’4496 in [relapsed or refractory] LBCL,” Matthew Ku, MBBS, FRACP, RACP, FRCPA/RCPA, PhD, concluded.

JNJ’4496 (JNJ-90014496) at the recommended phase 2 dose (RP2D) of 75M CAR T cells demonstrated promising antitumor efficacy and safety in a small population of patients with relapsed or refractory large B-cell lymphoma (LBCL), according to data from a phase 1b trial (NCT05421663) shared at the 2025 European Hematology Association Congress.

The overall response rate (ORR) at the RP2D (n = 22) was 96% (95% CI, 77%-100%), with complete responses (CRs) observed in 77% and partial responses (PRs) in 18%. At all dose levels (n = 44), the ORR was 91% (95% CI, 78%-98%), with CRs observed in 75% and PRs in 16%.

Among patients who received the RP2D, in those who received 1 prior line of treatment (n = 10), the ORR was 100% (95% CI, 69%-100%), with CRs observed in 80% and PRs in 20%. In those who received 2 or more lines of treatment (n = 12), the ORR was 92% (95% CI, 62%-100%), with CRs observed in 75% and PRs in 17%.

It was noted that at all dose levels and the RP2D, high rates of CR were observed regardless of the number of prior lines of therapy.

At all doses, with a median follow-up of 8 months, the median time to CR was 1 month (range, 1-6), 87% of responses (95% CI, 71%-94%) lasted 3 months or longer, and 10 responses deepened from PR to CR. At the RP2D, with a median follow-up of 4 months, the median time to CR was 1 month (range, 1-3), 79% of responses (95% CI, 54%-92%) lasted 3 months or longer, and 5 responses deepened from PR to CR.

“Safety, efficacy, and [the] pharmacokinetic profile support 75M CAR-positive T cells as the RP2D of the CD19/CD20 CAR-T therapy, JNJ’4496, in a broad population of patients with [relapsed or refractory] LBCL,” stated presenting study author Matthew Ku, MBBS, FRACP, RACP, FRCPA/RCPA, PhD, a clinical and laboratory hematologist and the lymphoma stream lead at St Vincent’s Hospital, in the presentation.

A total of 51 patients were assigned to receive either weight-based CAR T cells at 2 mg/kg (n = 18), a fixed dose of 150 M CAR T cells (n = 8), or a fixed dose of 75 M CAR T cells, the RP2D (n = 25). At the investigator’s discretion, some patients were offered bridging therapy.

Eligible patients were adults with relapsed or refractory LBCL with histologically confirmed CD19 and/or CD20 expression, as well as measurable disease per Lugano criteria and 2 or more prior lines of therapy. Patients who were ineligible for autologous stem cell transplant were only required to have 1 prior line of treatment.

The trial’s primary end point was safety and RP2D. Secondary end points included preliminary efficacy related to the CR rate, ORR, and duration of response, as well as pharmacokinetics.

Treatment-emergent adverse events (TEAEs) of any grade were reported in 100% of patients at all doses and at the RP2D, and TEAEs of grade 3 or 4 were reported in 86% across all doses and 84% at the RP2D. The most common TEAEs of grade 3 or 4 at all doses were neutropenia (78%), leukopenia (22%), thrombocytopenia (20%), and anemia (20%); at the RP2D, they were neutropenia (72%), lymphopenia (16%), anemia (16%), and leukopenia (12%). A total of 6 deaths occurred, all of which were due to disease progression. Serious TEAEs were reported in 28% of the RP2D group.

Cytokine release syndrome (CRS) of any grade was experienced by 80% of those across all dose levels and 88% at the RP2D; at all dose levels, 53% were grade 1, 24% were grade 2, and 4% were grade 3. At the RP2D, 68% of events were grade 1 and 20% were grade 2. The most common supportive measure for CRS was tocilizumab (Actemra), given to 76% at all dose levels and 84% at the RP2D.

Immune-effector cell-associated neurotoxicity syndrome (ICANS) occurred in 16% and 8% of patients at all doses and the RP2D, respectively. At all dose levels, 8% and 8% of events were grade 1 and grade 3, and at the RP2D, 4% and 4% were grade 1 and grade 3. ICANS was concurrent with CRS in 14% and 8% of patients, respectively.

Regarding pharmacokinetics, CAR expansion and persistence were comparable at RP2D to those at higher doses, and at the RP2D median, t_max occurred slightly later at 14 days post-infusion. Efficacy was comparable across doses.

“These findings support further development of JNJ’4496 in [relapsed or refractory] LBCL,” Ku concluded.

Reference

Patel K, Rhodes JM, Mountjoy L, et al. A global phase 1b study of JNJ-90014496, a CD19/CD20 bi-specific chimeric antigen receptor (CAR) T-cell therapy, in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma. Presented at the 2025 European Hematology Association Congress; Milan, Italy. June 12-15, 2025. Abstract S239.