Cilta-cel CARTITUDE-4 Trial to be Unblinded After Meeting Primary End Point


Cilta-cel demonstrated a significant improvement in progression-free survival over standards of care.

The phase 3 CARTITUDE-4 clinical trial (NCT04181827), which is evaluating Janssen’s and Legend Biotech's ciltacabtagene autoleucel (cilta-cel; CARVYKTI) against standards of care (SOC) in the treatment of relapsed/refractory multiple myeloma (MM), will be unblinded according to an independent data monitoring committee recommendation following the study meeting its primary end point in a pre-specified interim analysis.1

CARTITUDE-4 is evaluating cilta-cel for the treatment of relapsed and lenalidomide-refractory MM against SOC pomalidomide, bortezomib, and dexamethasone (PVd) and daratumumab, pomalidomide, and dexamethasone (DPd). The chimeric antigen receptor (CAR) T-cell therapy demonstrated a significant improvement in progression-free survival (PFS), the study's primary end point, over PVd and DPd. 

“The CARTITUDE-4 study represents the first phase 3 program in our comprehensive clinical development strategy for CARVYKTI, and further demonstrates our commitment to advance the treatment of patients with relapsed/refractory MM,” Jordan Schecter, MD, vice president, Clinical Development Cellular Therapy Program, Janssen Research & Development, LLC, said in a statement regarding the news.1 “We look forward to the presentation of the data from the CARTITUDE-4 study at a future medical meeting.”

CARTITUDE-4 enrolled 419 patients aged 18 years and older who had received between 1 and 3 prior lines of therapy for MM, including a proteasome inhibitor and an immunomodulatory drug. Participants were required to have measurable disease at screening; to have documented evidence of progressive disease according to International Myeloma Working Group criteria based on investigator determination within 6 months of their last regimen; to be refractory to lenalidomide according to study-specific criteria; and to meet a set of study-specific clinical laboratory value requirements. Patients who had previously been treated with any CAR T-cell therapy; those who had previously been treated with B-cell maturation antigen (BCMA)-targeting therapy; and those experiencing ongoing toxicity from previous anticancer therapy that had not resolved to baseline levels or to grade 1 or less, excepting alopecia, were excluded from participation. Additional exclusion criteria related to other treatment history. Patients who had grade 1 peripheral neuropathy with pain or grade 2 or higher peripheral neuropathy were not eligible to receive PVd in the trial but could receive DPd. 

Among the trial’s numerous secondary end points are complete response rate, overall minimal residual disease negative rate, overall survival, overall response rate, time to worsening of symptoms, and incidence and severity of adverse events. The trial has an estimated completion date of April 10, 2026. 

Cilta-cel previously demonstrated positive results in the phase 2 CARTITUDE-2 clinical trial (NCT04133636), including a 100% overall response rate in patients who had experienced early relapse after initial treatment for MM.2 CGTLive previously spoke with Niels van de Donk, MD, PhD, professor, cancer immunology and hematology, Amsterdam University Medical Centers, about data from CARTITUDE-2.

"Cilta-cel has now shown efficacy in early relapse and end stage patients...,” van de Donk said in the interview. “Because of the high efficacy of cilta-cel in high-risk populations and end stage myeloma, cilta-cel is not only moving to 1 to 3 prior lines, but there are also now several studies that will soon start enrolling patients in the first line. We hope to see that cilta-cel is really superior to autologous stem cell transplant and will improve the clinical outcomes of newly diagnosed myeloma patients.”

1. Janssen announces unblinding of phase 3 CARTITUDE-4 study of CARVYKTI (cilta-cel) as primary endpoint met in treatment of patients with relapsed and refractory multiple myeloma. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. January 27, 2023. Accessed January 27, 2023. 
2. van de Donk NWCJ, Agha ME, Cohen AD, et al. Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2, cohort B. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Poster #453.
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