Relapsed/refractory patients

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

On 6th 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 61st 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 6th 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 61st ASH meeting on Monday 9th 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 61st ASH meeting. Additionally, we will be publishing an interview with Deepu Madduri who spoke to us about the CARTITUDE-1 trial results.3

References
  1. PR Newswire. Janssen Announces BCMA CAR-T Therapy JNJ-4528 Granted U.S. FDA Breakthrough Therapy Designation for the Treatment of Relapsed or Refractory Multiple Myeloma. https://www.prnewswire.com/news-releases/janssen-announces-bcma-car-t-therapy-jnj-4528-granted-us-fda-breakthrough-therapy-designation-for-the-treatment-of-relapsed-or-refractory-multiple-myeloma-300970825.html. Published; December 6 2019, [Accessed 2019 Dec 07]
  2. Zhao W. H. et al., A phase I, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapse or refractory multiple myeloma. J Hematol Oncol. 2018 Dec 20; 11:141.DOI: 10.1186/s13045-018-0681-6.
  3. LEGEND Biotech. Initial Data from Phase 1b/2 Study of BCMA-Directed CAR-T Cell Therapy JNJ-4528 Show Early and High Responses in Advanced Relapsed or Refractory Multiple Myeloma. https://www.legendbiotech.com/pdf/ASH_2019_CARTITUDE1_Release_12072019.pdf Published; December 7 2019, [Accessed 2019 Dec 07]
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