Janssen presents initial results for BCMA CAR-T therapy JNJ-4528 showing early, deep and high responses in the treatment of relapsed or refractory multiple myeloma.
The initial results are from the Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety of JNJ-68284528 (JNJ-4528), an investigational B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy being evaluated in the treatment of patients with relapsed or refractory multiple myeloma.
The study enrolled patients who had received at least three prior lines of therapy or were double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD); had received a PI, IMiD and an anti-CD38 antibody. The CARTITUDE-1 study results, premiered at the American Society of Hematology (ASH) Annual Meeting, were featured as an oral presentation and highlighted in the official ASH press programme (Abstract #577).
Results from the Phase 1b portion of the CARTITUDE-1 study showed early and deep responses among patients (n=29) with a median of five prior multiple myeloma treatment regimens (range, 3–18) treated with JNJ-4528 (median administered dose 0.73×106 CAR+ viable T cells/kg). One hundred percent of patients achieved a response at a median follow-up of six months. Eighty-six percent of patients were triple-refractory to a PI, IMiD, and anti-CD38 antibody, 72 percent were penta-exposed, and 31 percent were penta-refractory. The overall response rate (ORR) included 69 percent of patients achieving a complete response (CR) or better (66 percent achieved a stringent CR); 86 percent of patients achieved a very good partial response (VGPR) or better; and 14 percent of patients achieved a partial response (PR). In addition, all 15 out of a total of 29 patients (100 percent evaluable) at the 10-5 sensitivity level were MRD negative at the latest sample available. At the median follow-up of six months, 27 of 29 patients were progression-free. Based on the Phase 1b results, a recommended Phase 2 dose of 0.75×106 CAR+ viable T cells/kg was confirmed.
“These initial results from the Phase 1b portion of the CARTITUDE-1 study highlight a compelling clinical profile for JNJ-4528 in heavily pre-treated patients with relapsed or refractory multiple myeloma,” said Deepu Madduri, M.D., Assistant Professor of Medicine, Hematology and Medical Oncology, Tisch Cancer Institute at Mount Sinai, New York, and principal study investigator. “With the CARTITUDE-1 expansion cohort fully enrolled and all patients dosed, we look forward to collecting additional efficacy and safety data to further define the profile of this BCMA-targeted CAR-T therapy.”
Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag, adds: “Janssen has a long-standing commitment to improving outcomes for patients with multiple myeloma and patients with relapsed or refractory disease remain in urgent need of new treatment options. We are excited to further explore the potential of JNJ-4528 and build on the early promising data seen in CARTITUDE-1.”
The most common adverse events (AEs) observed in the CARTITUDE-1 study were cytokine release syndrome (CRS) (93 percent); neutropenia (93 percent); anaemia (86 percent); and thrombocytopenia (86 percent). In patients who experienced grade 3 and above AEs (25 percent); the most common were neutropenia (93 percent); thrombocytopenia (69 percent); and anaemia (55 percent). A majority of patients (86 percent) experienced grade 1-2 CRS. One patient experienced grade 3 CRS and one patient died of complications from CRS at day 99. The median onset of CRS was generally predictable at seven days (range, 2-12) post-infusion, with a median duration of four days (range, 1-60).
“We are encouraged by the overall response reported in patients receiving JNJ-4528, results that build upon the LEGEND-2 study data as reported in Chinese patients and now show promise in U.S. patients,” said Sen Zhuang, M.D., Ph.D., Vice President, Oncology Clinical Development, Janssen Research & Development, LLC. “We are committed to advancing this novel BCMA-targeted CAR-T therapy through clinical development and bringing this immunotherapy to patients who are still in need of effective therapies to rapidly control their disease.”
JNJ-4528 is a structurally differentiated CAR-T with two BCMA targeting single domain antibodies. LCAR-B38M identifies the investigational product in China, sponsored by Janssen development partner, Legend Biotech. JNJ-4528 identifies the investigational product with the same CAR construct being studied in the U.S. and Europe.
Safety and efficacy results observed in the CARTITUDE-1 study were consistent with the LEGEND-2 study of LCAR-B38M, sponsored by Legend Biotech. In follow-up data from the LEGEND-2 study presented at ASH (Abstract #579), investigators reported the long-term response and safety profile for LCAR-B38M. Overall response rates of 88 percent were observed, with 46 percent of all-treated patients and 64 percent of the MRD-negative patients with CR remaining progression-free. The median progression-free survival (PFS) for all-treated patients was 20 months (range, 10–28); median PFS for MRD-negative patients with CR was 28 months (range, 20–31).
In a separate oral presentation (Abstract #928), data highlighting post-infusion CAR+ T cell expansion in the bone marrow and blood of patients enrolled in the CARTITUDE-1 study will be reported. While both CD4+ and CD8+ CAR+ T cells expanded in vivo, a preferential expansion of memory CD8+ CAR+ T cells was observed at peak expansion. These and other correlative studies are being conducted to better understand the immune mechanisms associated with response to JNJ-4528, and suggest that the high anti-myeloma activity of JNJ-4528 seen at a relatively low T cell dose is potentially related to its preferential and consistent in vivo expansion of CD8+ CAR+ T cells.