Study Evaluating the Safety and Efficacy of JCARH125 in Subjects With Relapsed and/or Refractory Multiple Myeloma

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 frame: From first infusion to up to aproximately 61 months

Population: All participants who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra), at dose level 600 x 10\^6 in phase 1 and in phase 1 Anakinra

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

Time frame: Day 1, 2, 3

Population: All participants who received at least one infusion of JCARH125 and at least one dose of anakinra as prophylactic intervention in phase 1 Anakinra

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.

Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)

Population: All participants who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) in phase 1 and in phase 1 Anakinra

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

Time frame: From day 1 to day 22 following JCARH125 infusion (Up to 21 days)

Population: All participants who have either experienced a DLT or were followed for the full DLT evaluation period in phase 1

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.

Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)

Population: All participants who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) in phase 1 and in phase 1 Anakinra

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

Time frame: 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)

Population: All participants who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

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

Time frame: From JCARH125 infusion to the first onset of Grade ≥2 CRS (Up to approximately 61 months)

Population: All participants with grade ≥2 CRS who received at least one infusion of JCARH125 (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) at dose level 600 x 10\^6 in phase 1 and in phase 1 Anakinra

AUC (0-28) of JCARH125 CAR T cells in the blood as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.

Time frame: From JCARH125 infusion through 28 days after the infusion

Population: All participants who have the necessary PK measurements to provide interpretable results for this specific parameter of interest

EQ-5D-5L is a standardized measure of health status that consists of descriptive system and Visual Analogue scale VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the dimensions are combined in a 5-digit number corresponding to response categories for successive dimensions using a scoring algorithm. The VAS system has endpoints labeled the best health you can imagine and the worst health you can imagine. The scale is numbered from 0 to 100 with 0 corresponding to the worst imaginable health state and 100 corresponding to the best imaginable health state. A high score represents a better level of quality of life

Time frame: Baseline and visit 24 month

Population: All participants who received at least one infusion of JCARH125 with baseline and post-baseline assessment at the respective visit in phase 2 only as prespecified in the protocol

The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures such as functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and other (dyspnoea, appetite loss, insomnia, constipation/diarrhea, and financial difficulties). Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Subscale scores are transformed to 0 to 100 scale, with higher scores on functional scales indicating better function and higher score on symptom scales indicating worse symptoms. Baseline is defined as the last non-missing measurement prior to JCARH125 infusion.

Time frame: Baseline and visit 24 month

Population: All participants who received at least one infusion of JCARH125 with baseline and post-baseline assessment at the respective visit in phase 2 only as prespecified in the protocol

QLQ-MY20 includes 20 questions across four scales: disease symptoms, treatment side-effects, future perspective, and body image. Questions used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale; higher score for the disease symptoms scale = higher level of symptomatology.

Time frame: Baseline and visit 24 month

Population: All participants who received at least one infusion of JCARH125 with baseline and post-baseline assessment at the respective visit in phase 2 only as prespecified in the protocol

CRR is defined as stringent complete response (sCR) or complete response (CR), 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

Time frame: 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)

Population: All participants who received conforming JCARH125 cell product at the recommended phase 2 dose (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion

DoCR is defined as the time from first response (stringent complete response (sCR), complete response (CR)) to the earlier date of progressive disease or death due to any cause. 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. Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.

Time frame: From first response to the date of progression or death due to any cause, whichever occurs first (Up to approixmately 61 months)

Population: All participants with sCR or CR who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

Total length of all intensive care unit (ICU) and non-ICU stays from JCARH125 Administration. ICU inpatient and non-ICU inpatient are not exclusive. Total length includes participants who had multiple hospitalization stays.

Time frame: From JCARH125 infusion to up to approximately 61 months

Population: All participants who received at least one infusion of JCARH125 with baseline and post-baseline assessment at the respective visit in phase 2 only as prespecified in the protocol

DoR is defined as the time from first response (stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR)) to the earlier date of progressive disease or death due to any cause. 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; 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. Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.

Time frame: From first response to the date of progression or death due to any cause, whichever occurs first (Up to approixmately 61 months)

Population: All participants with sCR, CR, VGPR, or PR who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

Cmax is the maximal concentration of JCARH125 CAR T cells in the blood after its infusion as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.

Time frame: From JCARH125 infusion through the day 29 visit

Population: All participants who have the necessary PK measurements to provide interpretable results for this specific parameter of interest

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.

Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)

Population: All participants who received at least one infusion of JCARH125 in phase 2 and in phase 2a

Pharmacokinetics persistence of JCARH125 CAR T cells in the blood as determined by quantitative polymerase chain reaction (qPCR) over time to detect the JCARH125 transgene. Persistence is defined as a transgene count greater than or equal to the lower limit of detection (LLOD).

Time frame: Day 29, 60, 90, 180, 270, 365, 545, 730

Population: All participants who have the necessary PK measurements to provide interpretable results for the specific parameters of interest

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.

Time frame: From the time of JCARH125 infusion to 90 days following the infusion (Up to 90 days)

Population: All participants who received at least one infusion of JCARH125 in phase 2 and in phase 2a

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

Time frame: 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 61 approximately months)

Population: All participants who received conforming JCARH125 cell product at the recommended phase 2 dose (and at least one dose of anakinra as prophylactic intervention for phase 1 Anakinra) and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 1 and in phase 1 Anakinra

OS is defined as the time from the JCARH125 infusion until death due to any cause.

Time frame: Form date of first infusion to the date of death due to any reason (Up to apprixamtely 61 months)

Population: All participants who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

PFS is defined as the time from JCARH125 infusion until the earliest date of disease progression or death from any cause. Progressive disease (PD) is defined as (1) Increase of ≥25% from lowest confirmed response in one or more of the following: Serum M-protein absolute increase ≥0.5 g/dL; Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL; Urine M protein absolute increase ≥200 mg/24 h; the difference between involved and uninvolved FLC levels absolute increase \>10 mg/dL; Bone marrow plasma-cell percentage irrespective of baseline status absolute increase ≥10%. (2) Appearance of a new lesion(s), ≥50% increase from nadir in SPDd of \>1 lesion, or ≥50% increase in the longest diameter of a previous lesion \>1 cm in short axis. (3) ≥50% increase in circulating plasma cells (minimum of 200 cells μL) if this is the only measure of disease.

Time frame: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)

Population: All participants who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

Number of participants with reasons for hospitalization from JCARH125 administration

Time frame: From JCARH125 infusion to up to approximately 61 months

Population: All participants who received at least one infusion of JCARH125 with baseline and post-baseline assessment at the respective visit in phase 2 only as prespecified in the protocol

TTCR is defined from JCARH125 infusion to the first document of stringent complete response (sCR) or complete response (CR). 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. Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.

Time frame: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)

Population: All participants with sCR or CR who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a

Tmax is the first study day the maximum observed concetration (Cmax) of JCARH125 CAR T cells in the blood is reached as determined by quantitative polymerase chain reaction (qPCR) to detect the JCARH125 transgene.

Time frame: From JCARH125 infusion through the day 29 visit

Population: All participants who have the necessary PK measurements to provide interpretable results for this specific parameter of interest

TTR is defined from JCARH125 infusion to the first document of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). 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; 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. Progressive disease is defined as (1) Increase of ≥25% from lowest confirmed response; (2) Appearance of a new lesion(s); (3) ≥50% increase in circulating plasma cells.

Time frame: Form date of first infusion to the date of disease progression, or death, due to any reason (Up to approximately 61 months)

Population: All participants with sCR, CR, VGPR, or PR who received conforming JCARH125 cell product at the recommended phase 2 dose and have measurable disease at the last disease assessment prior to receiving JCARH125 infusion in phase 2 and in phase 2a