Janssen and Legend Biotech's BCMA-Targeted CAR-T Therapy JNJ-4528 Demonstrates Robust Efficacy in Relapsed/Refractory Multiple Myeloma

Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson (JNJ), recently announced the latest results from the Phase Ib/II CARTITUDE-1 study (NCT03548207) of its BCMA CAR-T cell therapy, JNJ-4528. JNJ-4528 is an investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy.

This is an ongoing Phase Ib/II, open-label, multicenter study evaluating the efficacy and safety of JNJ-4528 in adult patients with relapsed or refractory multiple myeloma (RRMM). Among the enrolled patients, 97% were refractory to their last line of therapy, and 86% were triple-refractory, meaning their cancer did not respond or no longer responded to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti-CD38 antibodies. The primary objective of the Phase Ib portion was to determine the safety and dosage of JNJ-4528. The Phase II portion will assess the efficacy of JNJ-4528, with the overall response rate (ORR) as the primary endpoint.

The updated results released herein are from the long-term follow-up of the Phase Ib cohort (n=29): all patients demonstrated a therapeutic response to JNJ-4528, yielding an overall response rate (ORR) of 100%. The responses were profound and durable; at a median follow-up of 11.5 months, 86% of patients achieved stringent complete response (sCR), and 86% were alive and progression-free at 9 months.

Among the 100% overall response rate (ORR), 97% of patients achieved a very good partial response or better (≥VGPR), and 3% achieved a partial response (PR). Therapeutic responses were observed in 29 heavily pre-treated patients even with low-dose CAR-T cell administration (median dose: 0.72×10⁶ CAR+ viable T cells/kg). The median number of prior treatment regimens received by evaluated patients was 5 (range: 3–18); 86% of patients were triple-refractory, and 28% were penta-refractory. The median time to first response was 1 month (range: 1–3 months). Among evaluable patients (n=16), 81% achieved minimal residual disease (MRD) negativity (at a sensitivity of 10⁻⁵ or 10⁻⁶) at the time of first suspected complete response.

In the CARTITUDE-1 study, the most commonly observed adverse events (AEs) were neutropenia (100%) and cytokine release syndrome (CRS, 93%). Among patients experiencing Grade ≥3 AEs, the most common were neutropenia (100%), thrombocytopenia (69%), and leukopenia (66%). The median time to onset of CRS was 7 days post-infusion (range, 2–12 days), with most patients experiencing Grade 1–2 CRS; two patients experienced Grade 3 or higher CRS. Neurotoxicity consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in three patients (10%), including one patient (3%) with Grade 3 or higher toxicity. Three deaths were reported in the Phase Ib study: one due to CRS, one due to acute myeloid leukemia (unrelated to treatment), and one due to progressive disease.

Dr. Sen Zhuang, Vice President of Oncology Clinical Development at Janssen Research & Development, stated, “The latest data from the CARTITUDE-1 study demonstrate that JNJ-4528 has durable efficacy and a tolerable safety profile. We are continuing to advance the development of this novel CAR-T cell therapy with the aim of delivering differentiated immunotherapy for patients with multiple myeloma, many of whom have exhausted all available prior treatment options.”

Jesus G. Berdeja, MD, Principal Investigator of the study and Director of Myeloma Research at the Sarah Cannon Research Institute, stated, “The latest findings from the CARTITUDE-1 study demonstrate that JNJ-4528 provides durable therapeutic benefits for heavily pretreated patients with poor prognoses. We are encouraged not only by the relatively high rate of stringent complete responses but also by the progression-free survival observed in these patients.”

BCMA-Targeted Investigational Immunotherapies for Multiple Myeloma (Source: PMID: 31277554)

JNJ-4528 (LCAR-B38M) is an investigational chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of relapsed or refractory multiple myeloma (RRMM). The therapy features a structurally differentiated CAR-T construct incorporating two BCMA-targeting single-domain antibodies. CAR-T cell therapy is an innovative approach that harnesses the power of the patient’s own immune system to eliminate cancer cells. BCMA is a protein highly expressed on myeloma cells.

In December 2017, Janssen entered into an exclusive global license and collaboration agreement with Nanjing Legend Biotech (Legend Biotech) to develop and commercialize JNJ-4528 (LCAR-B38M). In May 2018, based on the results of the LEGEND-2 study, Janssen initiated a Phase Ib/II trial (NCT03548207) to evaluate the efficacy and safety of JNJ-4528 in adults with relapsed or refractory multiple myeloma.

In the United States, the FDA granted JNJ-4528 Breakthrough Therapy Designation in December 2019 and Orphan Drug Designation in February 2019. In the European Union, the European Commission granted JNJ-4528 Orphan Drug Designation in February 2020 and Priority Medicines (PRIME) status in April 2019.

Original Source: Janssen's BCMA CAR-T Therapy JNJ-4528 Showed Early, Deep and Durable Responses in Heavily Pretreated Patients with Multiple Myeloma

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