Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. The main aim of the study is to determine the safety and efficacy of JNJ-68284528 in various clinical settings. JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA). The study comprises of a Screening Phase (less than or equal to \[\<=\] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment); a Treatment Phase including a conditioning regimen followed by infusion of JNJ-68284528 and post-infusion assessments from Day 1 to Day 100 (participants who receive an infusion of JNJ-68284528 should continue all subsequent assessments); and a Post-treatment Phase (Day 101 and up to the end of each study cohort). Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, physical examination findings (including neurologic examination), assessment of cardiac function, immune effector cell-associated encephalopathy (ICE) score, handwriting assessment, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade. Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. For certain participants (those without measurable disease in serum or urine) efficacy will be assessed via imaging: positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI). The overall duration of the study is up to 2.5 years.
Inclusion Criteria:
- Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a
proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide
refractory per International Myeloma Working Group (IMWG) guidelines
- Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease
progression per IMWG criteria less than or equal to (<=) 12 months after treatment
with autologous stem cell transplantation (ASCT) or <=12 months from the start of
anti-myeloma therapy for participants who have not had an ASCT
- Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and
B-cell maturation antigen (BCMA)-directed therapy
- Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total
cycles of initial therapy, including induction, high-dose therapy, and ASCT with or
without consolidation
- Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of
prior therapy before enrollment is acceptable) and classified as high risk defined as
either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin
greater than or equal to (>=) 5.5 milligram per liter (mg/L) (via local or central
laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16),
t(14;20), 1q amplification (at least 4 total copies) in at least 20 percent (%) of the
total plasma cell population
- Cohort F:
- Participant must have a documented efficacy response of very good partial response
(VGPR) or better, without progressive disease prior to enrollment, as assessed per
IMWG 2016 criteria
- Received initial therapy as specified below. The dose/schedule of cycles administered
will be as per standard of care. It is acceptable for up to 1 cycle of the
protocol-specified regimens to be missing one of the listed agents (example, held due
to toxicity). Acceptable combinations include: At least 5 to 8 cycles of initial
therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The
dose/schedule of cycles administered will be as per standard of care or; at least 4 to
8 cycles of initial therapy with daratumumab, lenalidomide and dexamethasone (D-Rd)
or; at least 4 to 8 cycles of initial therapy with a carfilzomib-based triplet or
quadruplet regimen
- Cohorts A, B, C, E:
- Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram
per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours
- Light chain multiple myeloma in whom only measurable disease is by serum free light
chain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormal
serum immunoglobulin kappa lambda FLC ratio
- Cohort A: For participants with neither serum nor urine measurable disease, baseline
positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic
resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A
minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter
(cm)*1 cm is required
- Cohorts B, C: For participants with neither serum nor urine measurable disease,
baseline positron emission tomography/ computed tomography (PET/CT) or whole body
magnetic resonance imaging (MRI) may be used to satisfy the measurable disease
criteria
- Cohorts A, B, C, D, E, F: Eastern Cooperative Oncology Group (ECOG) performance status
grade of 0 or 1
Exclusion Criteria:
- Cohorts A, B, D, F: Any therapy that is targeted to BCMA
- Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T)
therapy directed at any target
- Cohorts A, B, C, D, F:
- Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or
to Grade 1 or less except for alopecia or peripheral neuropathy
- Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone
within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis
- Serious underlying medical condition, such as (a) evidence of active viral or
bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic
fungal infection; (b) active autoimmune disease or a history of autoimmune disease
within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d)
any history of Parkinson's disease or other neurodegenerative disorder
- Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system
(CNS) involvement or exhibits clinical signs of meningeal involvement of multiple
myeloma
