Legend Biotech Corporation, announced the updated results from the Janssen sponsored Phase 1b/2 CARTITUDE-1 study (NCT03548207) evaluating the efficacy and safety of JNJ-68284528 (JNJ-4528) in multiple myeloma.
There is something interesting about the drug, JNJ-4528 and its Phase 1b / 2 study on CARTITUDE-1. We Mellalta Meets, would like to shed some light on the topic.
Interesting Mechanism –BCMA
JNJ‑4528 is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapy. It is structured differently than other anti‑BCMA CAR-T therapies as it contains 2 BCMA‑targeting single‑chain antibodies which are designed to confer affinity, basically binding it to different places in BCMA, and perhaps lessening the potential for escape.
Multiple myeloma is the most lethal and currently an incurable blood cancer which starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.
Effective Results from ASCO 2020
The ongoing Phase 1b/2 study of CARTITUDE-1 (NCT03548207), is an open-label, multicenter study evaluating the safety and efficacy of JNJ-4528 for adults with relapsed or refractory multiple myeloma. The patients were dosed with 72×106 CAR‑viable T-cells per kg, heavily treated with median of 5 lines of prior therapy.
After analyzing the data of 11.5 months, the study demonstrated 100% overall response rate, 86% stringent complete response rate and a 9-month progression free survival rate of 86%. With 16 patients in CR available for MRD assessments, 81% were MRD‑negative at 10‑5 or better, and 69% at 10‑6 with PFS as 86% after 9 months. So, no unusual safety signals were as observed in the study.
Jesus Berdeja, MD, Sarah Cannon Research Institute, Nashville, Tennessee
What we can conclude is that we are learning more from these studies about the effectiveness, along with the toxicity profiles, it lends itself well to hopefully expanding it to different patients and not just the relapsed/refractory.
Deepu Madduri, MD, Associate Director, Cellular Therapy Service, and Director of Clinical Operations with the Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai.
Madduri noted that this heavily pretreated population has a high unmet medical need, with a median overall survival of less than 1 year. “We really need a product that we can give to these patients that will [induce] deep, sustained responses.”
Commenting on the efficacy findings, Madduri said, “Every single patient expanded their T cells,” adding, “What we think makes this product unique is the preferential expansion of the CD8+ central memory phenotype. CD8 cells are used to kill myeloma cells [and] these central memory cells, we think, have a way of not getting exhausted as often and having sustained effector function.”
Backed up by USFDA and EMA
JNJ‑4528 received breakthrough therapy designation from USFDA for the treatment of patients with relapsed/refractory multiple myeloma and Prime designation from EMA. The designation will accelerate the development and regulatory review of the anti-BCMA CAR-T treatment in this setting
With the phase 2/3 study in progress, they are more attentive to treatment with this product in the different phases of the disease, perhaps moving it earlier. The randomized phase 3 study on patients who had had at least 2 previous lines of therapy will also be initiated in the near future.
There will also be a study, or one of the study cohorts, to examine a consolidation with JNJ 4528 in patients with high risk disease as part of their initial treatment.