The U.S. FDA grants JNJ 4528 breakthrough therapy designation

On 6^th December 2019, the United States (U.S.) Food & Drug Administration (FDA) announced it had granted breakthrough therapy designation to JNJ 4528 for the treatment of relapsed/refractory multiple myeloma (RRMM). JNJ 4528 is anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy. This approval was based on results from the LEGEND-2 and CARTITUDE-1 trials. JNJ 4528 was previously granted orphan drug designation by the U.S. FDA in February 2019, and PRIME designation by the European Medicines Agency (EMA) in April 2019.¹

LEGEND-2

JNJ 4528, known as LCAR-B38M in China, was first investigated in the phase I LEGEND-2 trial. In December 2018, the results of this trial were published in the Journal of Hematology & Oncology. This analysis reported the outcomes of 57 patients with RRMM who had received a median of three prior lines of therapy. Efficacy was promising with 88% of patients achieving an overall response; 68% complete response (CR), 5% very good partial response (VGPR), and 14% partial response (PR). Additionally, 63% of patients achieved minimal residual disease (MRD)-negative disease.² Read more about the results from LEGEND-2 on the Multiple Myeloma (MM) Hub here.

In China, the phase II CARTIFAN-1 study (NCT03758417) is ongoing to further evaluate the efficacy of LCAR-B38M in patients with RRMM.¹ Additionally, data from LEGEND-2 with a longer follow-up is due to be presented at the 61^st American Society of Hematology (ASH) meeting (abstract #579) in December.³

CARTITUDE-1

The phase Ib/II CARTITUDE-1 (NCT03548207) trial is investigating JNJ 4528 in patients with RRMM in the US.³

Study design³

• Patients with RRMM who have received three or more prior lines of therapy or are double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), have received a PI, IMiD and anti-CD38 antibody, and who progressed within 12 months of their last line of therapy
• The safety and dose was informed by the phase I LEGEND-2 trial
• Primary objective of phase II portion: evaluate efficacy
  • Primary endpoint: overall response rate (ORR)

Patient characteristics³

• Patients with RRMM, n=29
• Median patient age: 60 years (50 –75)
• Median prior lines of therapy: 5 (3–18)
• Median administered dose: 0.73 x 10⁶ CAR T cells/kg
• 86% of patients were triple-refractory to a PI, IMiD and anti-CD38 antibody
  • 72% were penta-exposed
  • 31% were penta-refractory

Efficacy³ at data cut-off of 6^th November 2019

• ORR: 100%
  • ≥ CR: 69%
    • Stringent CR (sCR): 66%
    • 100% of patients achieving CR were MRD-negative at 10^-5
  • ≥ VGPR: 17%
  • PR: 14%
• Median follow-up of six months: 27/29 were progression-free

Safety³

• Most common adverse events:
  • Cytokine release syndrome : 93%
    • Grade I-II: 80%
    • One grade III event
    • One grade V event
    • Median time to onset: seven days
  • Neutropenia: 93%
  • Thrombocytopenia: 86%
  • Anemia: 86%

The results of this study are due to be presented at the 61^st ASH meeting on Monday 9^th December 2019 (abstract #577). The MM Hub will be covering the LEGEND-2 and CARTITUDE-1 sessions via social media and as written articles following the 61^st ASH meeting. Additionally, we will be publishing an interview with Deepu Madduri who spoke to us about the CARTITUDE-1 trial results.³