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JCARH125

Phase 1

Multiple Myeloma | Monoclonal antibody | Other |Bristol-Myers Squibb Company|Last Updated: May 24, 2024

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Trial Design

CONTROLLEDDMC
Total Trials1
Total Enrollment165

FDA Designations

No designations recorded

Clinical trial landscape

JCARH125 · 1 trial · 1 indication

Phase 1 1
NCT03430011Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple MyelomaMultiple Myeloma
COMPLETED165 Analytics
PHASE1COMPLETED
Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma
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Study Endpoints

Primary Endpoints

Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1
From day 1 to day 22 following JCARH125 infusion (Up to 21 days)

DLT is defined as adverse events (AEs) that occur within 21 days following JCARH125 infusion and meet any of the following criteria: * Treatment-emergent Grade ≥3 allergic reactions related to JCARH125; * Treatment-emergent Grade 3 seizures, regardless of attribution, that do not resolve to Grade ≤2 within 3 days in participants who have no evidence of central nervous system (CNS) involvement of Multiple Myeloma or other CNS pathology; * Treatment-emergent autoimmune toxicity Grade ≥3, regardless of attribution (excluding B-cell aplasia); * Treatment-emergent Grade 3 CRS that does not resolve to Grade ≤2 within 72 hours; * Any other treatment-emergent Grade 3 AE related to JCARH125 that does not resolve to Grade ≤2 within 7 days; * Any treatment-emergent Grade 4 AE related to JCARH125 that does not resolve to Grade ≤2 within 7 days; * Treatment-emergent Grade 4 Cytokine Release Syndrome of any duration; * Any treatment-emergent Grade 5 toxicity not due to the underlying malignancy

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity in Phase 1 and Phase 1 Anakinra
From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)

TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment will not be considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening; and Grade 5=death.

Number of Participants With Clinically Significant Laboratory Abnormalities by Severity in Phase 1 and Phase 1 Anakinra
From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)

Clinically significant laboratory abnormalities are assessed by investigator and are reported as treatment-emergent adverse event (TEAE). TEAE is defined as an AE that starts any time from initiation of JCARH125 administration through and including 90 days following the JCARH125 infusion graded by Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Any AE occurring after the initiation of another anticancer treatment is not considered a TEAE. Grade 3=Severe; Grade 4=Life-threatening.

Number of Participants Receiving Prophylactic Anakinra With Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra
From first infusion to up to aproximately 61 months

Number of participants receiving prophylactic anakinra with grade ≥ 2 CRS relative to the number of participants treated at the recommended Phase 2 dose (RP2D) in the Phase 1 dose escalation portion of the trial with grade ≥ 2 CRS. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening

Time to Onset of Grade ≥2 Cytokine Release Syndrome (CRS) in Phase 1 and Phase 1 Anakinra
From JCARH125 infusion to the first onset of Grade ≥2 CRS (Up to approximately 61 months)

Time to first onset of Grade ≥2 CRS in participants receiving prophylactic anakinra relative to onset of Grade ≥ 2 CRS in participants treated at the RP2D(s) in the Phase 1 dose escalation portion of the trial. Time to onset is calculated from the latest JCARH125 infusion prior to the first onset of Grade \>= 2 CRS. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening

Number of Participants Receiving Prophylactic Anakinra With no Cytokine Release Syndrome (CRS) Occurring on Days 1-3 in Phase 1 Anakinra
Day 1, 2, 3

The number of participants receiving prophylactic anakinra with no CRS occurring on study days 1, 2, or 3. CRS grade is defined by the most severe symptom (excluding fever). Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening

Overall Response Rate (ORR) in Phase 2 and Phase 2a
From the time of the JCARH125 infusion until disease progression, end of study, or the start of another anticancer therapy or stem cell transplant (Up to aproximately 61 months)

ORR is defined as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), according to IMWG criteria. Participants without any reported disease response assessments will be considered non-responders. sCR=complete response plus normal free light chain ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry; CR=negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow aspirates. When the only method to measure disease is by serum FLC levels, CR can be defined as a normal FLC ratio of 0.26 to 1.65; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein level plus urine M-protein level \< 100 mg/24 h; PR=≥ 50% reduction of serum M protein plus reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg/24 h

Secondary Endpoints

Maximum Observed Concentration (Cmax)
From JCARH125 infusion through the day 29 visit
Time to Maximum Observed Concentration (Tmax)
From JCARH125 infusion through the day 29 visit
Area Under the Concertation-Time Curve (AUC) From Time Day 1 to Day 29 [AUC (0-28 Days)]
From JCARH125 infusion through 28 days after the infusion
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
JCARH125EXPERIMENTALSubjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by a single dose of JCARH125
JCARH125 + anakinraEXPERIMENTALSubjects will receive a course of lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by prophylactic treatment with anakinra and a single dose of JCARH125

Interventions

NameTypeDescription
JCARH125BIOLOGICALParticipants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by one dose of JCARH125 administered intravenously (IV).
JCARH125 + anakinraBIOLOGICALParticipants will undergo leukapheresis to isolate PBMCs for the production of JCARH125. During JCARH125 production, participants may receive bridging chemotherapy for disease control. Following successful generation of JCARH125 product, participants will receive a course of lymphodepleting chemotherapy followed by two doses of anakinra administered subcutaneously and one dose of JCARH125 administered IV. Subjects receive anakinra for 5 consecutive days following JCARH125 infusion.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites20

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...

Countries:United States
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Competitive Landscape -Multiple Myeloma 221 trials

Top 20 of 25 competitors

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GSK plc Sponsored ADRGSK17PHASE3Belantamab mafodotin, Pomalidomide, Dexamethasone, Bortezomib
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Regeneron Pharmaceuticals, Inc.REGN11PHASE3Linvoseltamab, Carfilzomib, Daratumumab, Dexamethasone, Pomalidomide
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Incyte CorporationINCY2PHASE1Ruxolitinib, Lenalidomide, Methylprednisolone
Moderna, Inc.MRNA2PHASE1mRNA-2808
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