SOMERSET, N.J.– Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global, clinical-stage biotechnology company developing and manufacturing novel therapies, announced today new and updated results from the CARTITUDE clinical development program studying ciltacabtagene autoleucel (cilta-cel) in the treatment of multiple myeloma, which were presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition. Cilta-cel is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy being studied as a one-time treatment for multiple myeloma.
CARTITUDE-1 Data Continues to Support the Potential of Cilta-cel
In an oral presentation (Abstract #549), longer-term results from the Phase 1b/2 CARTITUDE-1 study in 97 patients with relapsed or refractory multiple myeloma (RRMM) continued to show a very high overall response rate (ORR) of 98 percent. After 21.7 months of follow-up, 83 percent of patients treated with cilta-cel achieved a stringent complete response (sCR)—higher than the 67 percent sCR rate reported at a median of ~1 year of follow up.1 Further, 95 percent of patients achieved a very good partial response (VGPR) or better. Median progression-free survival (PFS) and median overall survival (OS) have not been reached, but the 2-year PFS rate was 61 percent (95 percent Confidence Interval [CI], 48.5–70.4) and the 2-year OS rate was 74 percent (95 percent CI, 61.9–82.7). Of the 61 patients evaluable for minimal residual disease (MRD), 92 percent were MRD-negative at the 10-5 cutoff threshold. The two-year PFS rates in patients with sustained MRD negativity for ≥6 and ≥12 months were 91 percent (95 percent CI, 67.1–97.8) and 100 percent, respectively.
The median time to first response was one month (range, 0.9-10.7); the median time to best response was 2.6 months (range, 0.9-17.8); and the median time to complete response or better was 2.9 months (range, 0.9-17.8).1 The longer-term data showed no new safety signals and there were no new events of cilta-cel-related neurotoxicity or movement and neurocognitive treatment emergent adverse events (TEAEs) (MNT) reported since the median ~1 year follow-up. Implementation of MNT mitigation measures has decreased the incidence rate to 0.5 percent in the CARTITUDE clinical development program.
In the 18-month follow-up data previously presented at ASCO 2021, the most common hematologic adverse events (AEs) observed were neutropenia (96 percent); anemia (81 percent); thrombocytopenia (79 percent); leukopenia (62 percent); and lymphopenia (53 percent).2 At 18 months, cytokine release syndrome (CRS) of any grade was observed in 95 percent of patients with a median duration of four days (range, 1-97), and median time to onset of seven days (range, 1-12). Of the 92 patients with CRS, 95 percent experienced Grade 1/2 events and CRS resolved in 91 patients (99 percent) within 14 days of onset. Neurotoxicity of any grade was observed in 21 percent (n=20) of patients, with Grade 3 or higher neurotoxicity observed in 10 percent (n=10) of patients.
“Patients with heavily pre-treated multiple myeloma often have exhausted available treatment options and face poor prognoses. The updated results from the CARTITUDE-1 trial continue to suggest that cilta-cel may provide this patient population with lasting deep and durable responses,” said Thomas Martin, M.D., director of clinical research, clinical professor of medicine, Adult Leukemia and Bone Marrow Transplantation Program, interim Division Chief, co-director, Myeloma Program and co-leader, Hematopoietic Malignancies Program, at UCSF Helen Diller Family Comprehensive Cancer Center, and principal study investigator. “As a one-time infusion that shows potential to improve long-term survival and offer patients a break in ongoing treatments, cilta-cel may offer hope to patients, caregivers and physicians.”
In a subgroup analysis of CARTITUDE-1 (Abstract #3938), responses to cilta-cel were durable up to 2 years in most subgroups of patients with heavily pretreated RRMM.3 An ORR range of 95 to 100 percent was observed in patients across all subgroups, including those with high-risk cytogenetics, International Staging System (ISS) stage III, baseline bone marrow cells ≥60 percent, and presence of baseline plasmacytomas. In patients with ISS stage III, high risk cytogenetics and with baseline plasmacytomas, median duration of response, 2-year PFS and OS appeared lower. The cilta-cel safety profile across the subgroups was consistent with the overall population, with no new safety signals.
Additionally, an adjusted indirect comparison of CARTITUDE-1 patient outcomes relative to standard-of-care therapies in real-world clinical practice (RWCP) was also featured in an oral presentation (Abstract #550).4 The adjusted comparisons versus CARTITUDE-1 demonstrate a significantly improved ORR, complete response or better (≥CR), VGPR or better (≥VGPR), PFS and OS for the patients receiving cilta-cel compared to a diverse set of RWCP. Although patients treated with cilta-cel experienced more adverse events (AEs), including Grade 3/4 events, as compared to RWCP, overall safety profile was manageable.
CARTITUDE-2 Data Explores Use of Cilta-cel in Earlier-Line MM Settings
The Phase 2 multicohort CARTITUDE-2 study is evaluating cilta-cel safety and efficacy in various clinical settings for patients with multiple myeloma. Updated data from Cohort A of the study examined the efficacy and safety of cilta-cel in 20 patients with progressive multiple myeloma after 1-3 prior lines of therapy and who are lenalidomide-refractory (Abstract #3866).5 At a longer median follow-up of 14.3 months, patients experienced early and deep responses with a manageable safety profile consistent with the CARTITUDE-1 study. ORR was 95 percent, which included 85 percent of patients achieving CR or better and 90 percent achieving VGPR or better. The median time to first response was one month (range, 0.7-3.3) and the median time to best response was 2.6 months (range, 0.9-7.9). The 6-month and 12-month PFS rates were 95 percent (95 percent CI, 69.5-99.3) and 84 percent (95 percent CI, 59.1-94.7), respectively. Of the 13 patients with MRD evaluable samples at the 10-5 cutoff threshold, 92 percent (95 percent CI, 64.0-99.8) were MRD negative.
The first data from Cohort B was also presented at ASH 2021 (Abstract #2910).6 Cohort B included 19 patients who were in early relapse after initial therapy that included a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). Data showed early and deep responses with a manageable safety profile. At a median follow-up of 10.6 months, ORR was 95 percent, which included 79 percent of patients achieving CR or better and 90 percent of patients achieving VGPR or better. The median time to first response was one month (range, 0.9-2.6) and the median time to best response was 2.5 months (range, 0.9-11.8). The 6-month and 12-month PFS rates were 90 percent (95 percent CI, 64.1-97.3) and 84 percent (95 percent CI, 57.9-94.5), respectively. Of the 13 patients with MRD evaluable samples at the 10-5 cutoff threshold, 92 percent (95 percent CI, 64.0-99.8) were MRD-negative.
The safety profile seen in CARTITUDE-2 Cohorts A and B were consistent with data previously reported from CARTITUDE-1. CRS occurred in 95 percent of patients in Cohort A and 84 percent of patients in Cohort B, which were mostly grades 1/2 with median time to onset of 7-8 days and median duration of ~4 days.
“The new and updated longer-term data for CARTITUDE-1 and Cohorts A and B of CARTITUDE-2 shows that responses continue to be deep and durable over time and illustrate the potential of cilta-cel to provide a new treatment option for those patients that need it the most,” said Ying Huang, PhD, CEO and CFO of Legend Biotech. “We are excited to continue to present these strong efficacy and safety results as we work toward the first regulatory approval for cilta-cel and from our robust cell therapy pipeline.”
