Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
This is an open-label, multicenter, Phase 1/2 study to determine the safety and efficacy of
 JCARH125, a CAR T-cell product that targets B-cell maturation antigen (BCMA), in adult
 subjects with relapsed and/or refractory multiple myeloma. The study will include a Phase 1
 part to determine the recommended dose of JCARH125 in subjects with relapsed and/or
 refractory multiple myeloma, followed by a Phase 2 part to further evaluate the safety and
 efficacy of JCARH125 at the recommended dose. The safety and tolerability of JCARH125 in
 subjects who receive prophylactic treatment with anakinra will be evaluated in a separate
 Phase 1 cohort. The antitumor activity of JCARH125 in subjects who have been previously
 treated with BCMA-directed therapy will be evaluated in separate Phase 2a cohorts.
Key Inclusion Criteria:

 1. Diagnosis of multiple myeloma (MM) with relapsed and/or refractory (R/R) disease.
 Participants must have received at least 3 prior anti-myeloma treatment regimens.
 Participants must have previously received all of the following therapies and must be
 refractory to the last line of therapy prior to entering the study (not applicable to
 Phase 2a):

 1. Autologous stem cell transplant

 2. A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide,
 pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib),
 either alone or in combination

 3. Anti-CD38 (eg, daratumumab) as part of a combination regimen or as a monotherapy

 Subjects who have received prior allogeneic stem cell transplant or donor lymphocyte
 infusion at least 100 days before enrollment with no signs of acute or chronic
 graft-versus-host disease (GVHD) will be considered eligible. Subjects who were not
 candidates to receive one or more of the above treatments (ie, contraindicated) are
 eligible.

 2. Subjects must have measurable disease.

 3. Subject must be willing to provide fresh bone marrow biopsy samples during Screening
 (and prior to study treatment, if required).

 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

 5. Adequate renal, bone marrow, hepatic, pulmonary, and cardiac function

 6. Phase 2a cohorts only - Subjects with R/R MM who have been previously treated with
 prior BCMA-directed anti-myeloma therapy, achieved at least a partial response (PR)
 and progressed on the following treatment:

 1. Subjects who have received prior BCMA-directed CAR T-cell therapy. The last CAR
 T-cell therapy must have been received at least 6 months prior to JCARH125
 screening.

 2. Subjects who have received prior BCMA-directed T-cell engager therapy.

 3. Subjects who have received prior BCMA-directed antibody-drug conjugate therapy.

 Exclusion Criteria:

 1. Subjects with known active or history of CNS involvement by malignancy

 2. Subjects with solitary plasmacytoma; active or history of plasma cell leukemia (PCL);
 Waldenstrom's macroglobulinemia; Polyneuropathy, Organomegaly, Endocrinopathy,
 Monoclonal plasmaproliferative disorder, Skin changes (POEMS) syndrome; or symptomatic
 amyloidosis

 3. Subjects who are considered eligible to receive and have not refused an autologous
 stem cell transplant

 4. History of another primary malignancy that has not been in remission for at least 3
 years. The following are exempt from the 3-year limit: non-melanoma skin cancer,
 curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or
 a squamous intraepithelial lesion on Pap smear, and in situ breast cancer that has
 been completely resected.

 5. Require systemic immunosuppressive therapies (eg, calcineurin inhibitors,
 methotrexate, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such
 as anti-IL-6 or anti-IL-6 receptor [IL-6R])

 6. Prior CAR T-cell or other genetically-modified T-cell therapy (not applicable for
 subjects enrolled in Phase 2a cohorts)

 7. Prior treatment with a BCMA-targeted agent (not applicable for subjects enrolled in
 Phase 2a cohorts)

 8. History or presence of clinically relevant CNS pathology such as epilepsy, seizure,
 paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease,
 cerebellar disease, organic brain syndrome, or psychosis

 9. Untreated or active infection at time of initial screening, at the time of
 leukapheresis, within 72 hrs before lymphodepletion, or 5 days before JCARH125
 infusion.

 10. History of any of the following cardiovascular conditions within 6 months of
 screening: Class III or IV heart failure as defined by the New York Heart Association
 (NYHA), myocardial infarction, unstable angina, uncontrolled or symptomatic atrial
 arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac
 disease

 11. Subjects with known hypersensitivity to E Coli-derived proteins (only applicable to
 subjects in Phase 1 Anakinra Cohort)

 12. History of severe immediate hypersensitivity reaction to any of the protocol-mandated
 or recommended agents used in this study