a study of jnj-68284528, a chimeric antigen receptor t cell (car-t) therapy directed against b-cell maturation antigen (bcma) in participants with multiple myeloma

Conditions: Multiple Myeloma

Summary: the purpose of this study is to evaluate the overall minimal residual disease (mrd) negative rate of participants who receive jnj-68284528.


Eligibility criteria:
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 milligrams 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 * cohort g: not considered for high-dose chemotherapy with autologous stem cell transplantation (asct) due to: a) ineligibility due to advanced age; or b) ineligibility due to presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with asct; or c) subject refusal of high-dose chemotherapy with asct as initial treatment * cohort h: considered a candidate for high-dose chemotherapy with asct as initial treatment * cohorts a, b, c, e, g, h: * serum monoclonal paraprotein (m-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dl) or urine m-protein level \>=200 milligrams (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, g, h: 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 * cohorts f, g, and h: active malignancies (that is, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. the only allowed exceptions are: a) non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured; b) skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; c) non-invasive cervical cancer treated within the last 24 months that is considered completely cured; d) localized prostate cancer (n0m0): with a gleason score of greater than or equal to (=\>)6, treated within the last 24 months or untreated and under surveillance, with a gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, or history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence, e) breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence; f) malignancy that is considered cured with minimal risk of recurrence * cohorts e, g, and h: frailty index of \>= 2 according to myeloma geriatric assessment score

Keywords: cellular therapy car-t therapy bcma car-t