JNJ-68284528 ( JNJ-4528 ) is a chimeric antigen receptor T ( CAR-T ) cell therapy containing 2 B-cell maturation antigen ( BCMA)-targeting single-domain antibodies.
Researchers have presented updated CARTITUDE-1 phase 1b results with longer follow-up.
Patients had multiple myeloma per IMWG criteria, measurable disease, received 3 or more prior regimens or were double refractory to a PI and IMiD, and received anti-CD38 antibody.
Cyclophosphamide 300 mg/m2 + Fludarabine 30 mg/m2 over 3 days were used for lymphodepletion.
JNJ-4528 ( median, 0.73x106 CAR+ viable T cells/kg ) was given as a single infusion.
Cytokine release syndrome ( CRS ) was graded by Lee et al 2014 and neurotoxicity by CTCAE, v 5.0 and ASTCT grading.
Response was assessed per IMWG criteria.
As of 17 Jan 2020, median follow-up is 9 months ( 3–17 ). Phase 1b enrollment is complete ( n=29 treated; median 5 [ 3–18 ] prior lines, 76% penta-exposed, 86% triple-refractory, 31% penta-refractory, 97% refractory to last line of therapy ).
Most frequent adverse events were neutropenia ( 100% ), CRS ( 93% ), and thrombocytopenia ( 93% ).
Grade greater than or equal to 3 hematologic adverse effects were neutropenia ( 100% ), thrombocytopenia ( 69% ), and leukopenia ( 59% ).
27 ( 93% ) patients had CRS; 25 grade 1–2, 1 grade 3, and 1 grade 5 ( day 99 subsequent to dose-limiting toxicity of prolonged grade 4 CRS ).
Median time to onset of CRS was 7 days ( 2–12 ). 4 patients had treatment-related neurotoxicity: 3 grade 1–2 and 1 grade 3.
Objective response rate ( ORR ) was 100%, with 22 ( 76% ) stringent complete responses ( sCRs ), 6 ( 21% ) very good partial responses ( VGPRs ), and 1 ( 3% ) PR.
Median time to greater than or equal to CR was 2 months ( 1–9 ).
26/29 patients are progression-free, with 6-months progression-free survival rate of 93% and longest response ongoing at 15 months.
1 death due to CRS and 1 to acute myeloid leukemia ( not treatment-related ) occurred during the study.
All 16 patients ( 14 sCR, 2 VGPR ) evaluable at 6 months were minimal residual disease negative at 10−5 or 10−6.
JNJ-4528 CAR+ T cell expansion peaked between day 10–14.
At 6-month individual follow-up, 22/28 patients had JNJ-4528 CAR+ T cells below the level of quantification ( 2 cells/µL ) in peripheral blood, suggesting CAR-T persistence in peripheral blood did not seem to correlate with deepening of response.
At peak expansion, preferential expansion of CD8+ CAR-T cells with a central memory phenotype was observed in peripheral blood.
In conclusion, JNJ-4528 treatment led to responses in all patients. These responses were early, deep, and durable at a low dose of CAR-T cells with 26/29 ( 90% ) patients progression free at median 9-mo follow-up.
CRS was manageable in most patients, supporting outpatient dosing. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020