Initial safety data from an ongoing proof-of-concept trial of JCARH125, an investigational BCMA-targeting CAR T being developed by Juno Therapeutics/Celgene Corporation) in patients with relapsed/refractory multiple myeloma, were? presented by Sham Mailankody, MBBS, in an oral presentation at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, CA (Abstract #957).
The data from 44 patients in the EVOLVE trial further support our commitment to innovation in multiple myeloma clinical research…
The data reported from the multicenter, phase I/II EVOLVE trial (NCT03430011) includes patients who have been treated with JCARH125 in the dose escalation study.[2]
The primary objectives of the phase I portion of the trial are safety and identification of a recommended phase II dose. The patients enrolled in the study had to have received at least three prior lines of multiple myeloma therapy, including an autologous stem cell transplant for transplant eligible patients, a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Dose escalation is currently ongoing.
?We believe that cellular therapies targeting BCMA will play an important role in the future treatment of patients with multiple myeloma,? said Mark Gilbert, MD, Chief Medical Officer at Juno Therapeutics.
?These data from 44 patients in the EVOLVE trial further support our commitment to innovation in multiple myeloma clinical research,? Gilbert added.
At data cut off, 44 patients have been infused with JCARH125 in three dose escalation cohorts. These patients were heavily pretreated, with a median of seven prior lines of therapies (range, 3-23), and 77% had high-risk cytogenetics.
Adverse events
Seventy-one percent of patients experienced grade 1 and 2 cytokine release syndrome (CRS) with 9% of patients experiencing grade 3/4 CRS. In addition, 18% of patients experienced grade 1 and 2 neurological events with 7% of patients experiencing a grade 3/4 event. Other frequent grade 3/4 AEs included neutropenia (86%), anemia (50%), thrombocytopenia (43%) and infection (14%).
In this first report of JCARH125 data, the median follow up was only 11 weeks, yet among infused patients, the overall response rate (ORR) was 82%. At the lowest dose level of 50×106 CAR T cells, the ORR was 79% and 43% of patients achieved stringent complete response (sCR) or complete response (CR).
Conclusion
Based on the data from the trial, the researchers concluded that at initial lower dose levels, JCARH125 showed an acceptable safety profile with no DLTs reported thus far. Incidence of grade ? 3 NT was low and no grade ? 3 CRS has occurred with clear clinical activity. Although durability of response and response rate in a greater number of patients remain to be determined, early experience with JCARH125 support a favorable risk-benefit profile and rapid clinical development.
References
[1] Mailankody S, Htut M, Lee KP, Bensinger W, Devries T, Piasecki J, Ziyad S, Blake M, et al. JCARH125, Anti-BCMA CAR T-cell Therapy for Relapsed/Refractory Multiple Myeloma: Initial Proof of Concept Results from a Phase 1/2 Multicenter Study (EVOLVE). Oral presentation | American Society of Hematology. December 3, 2018.[Abstract]
[2] Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma (EVOLVE)
Last Editorial Review: December 4, 2018
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