A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma

NCT03548207 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: CR10848068284528MMY20012018-000121-32
• Study Type: interventional
• Target: 126
• Locations: 2 countries
• Sites: 21

Brief Summary

The purpose of the study is to characterize safety of JNJ-68284528 and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of JNJ-68284528 (Phase 2).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Number of Participants With Adverse Events as Per Severity

  An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

  Day 1 up to 45.2 months

• Phase 2: Overall Response Rate (ORR)

  ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (\>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to less than (\<) 200 milligrams (mg) per 24 hours. If the serum and urine M-protein were not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels was required in place of the M-protein criteria. If serum and urine M-protein were not measurable, and serum free light assay was also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) was required in place of M-protein, provided baseline bone marrow PC percentage was \>=30%. In addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas was also required.

  Day 1 up to 45.2 months

Secondary Outcomes (32)

• Phase 2: Number of Participants With Adverse Events (AEs) as Per Severity

  Day 1 up to 45.2 months

• Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of JNJ-68284528 Transgene

  Pre and post dose on Day 1, and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years)

• Phase 1b and Phase 2: Actual Sampling Time of Last Measurable Analyte Concentration (Tlast) of JNJ-68284528 Transgene

  Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years)

• Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 To Last Measurable Concentration (AUC0-last) of JNJ-68284528 Transgene

  Pre and post dose on Day 1; Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years)

• Phase 1b and Phase 2: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinite Time (AUC0-infinity) of JNJ-68284528 Transgene

  Pre and post dose on Day 1 and Days 2, 3, 7, 10, 14, 21, 28, 42, 56, 78, 100, then every 4 weeks up to 1 year, and at the time of progressive disease or at study completion for participants without progressive disease (up to approximately 2.5 years)

Study Arms (1)

JNJ-68284528

EXPERIMENTAL

After lymphodepletion JNJ-68284528 will be administered as a single infusion.

Biological: JNJ-68284528

Interventions

JNJ-68284528 BIOLOGICAL

JNJ-68284528 consist of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

JNJ-68284528

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
• Have measurable disease at Screening as defined by any of the following a) Serum monoclonal paraprotein (M-protein) level more than or equal to (\>=) 1.0 gram per deciliter(g/dL) or urine M-protein level \>=200 milligram per 24 hours (mg/24hr); or b) Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Have received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single lines of therapy a) Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease (PD) was the best response to the regimen
• Have received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody
• Participant must have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or within 12 months of their last line of therapy. Confirmation may be from either central or local testing. Also, participants with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

You may not qualify if:

• Have received prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
• Have received any therapy that is targeted to B-cell maturation antigen (BCMA)
• Have following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) less than or equal to (\<=) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction \[LVEF\] less than \[\<\]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (\<=) 8 weeks of apheresis)
• Received a cumulative dose of corticosteroids equivalent to \>= 70 mg of prednisone within the 7 days prior to apheresis
• Have received either of the following: a) An allogenic stem cell transplant within 6 months before apheresis. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD) b) An autologous stem cell transplant less than or equal to (\<=) 12 weeks before apheresis
• Have known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (21)

Mayo Clinic Cancer Center-Scottsdale

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55902, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Froedtert Memorial

Milwaukee, Wisconsin, 53226, United States

Location

University Hospital Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

Related Publications (11)

• Lopez-Munoz N, Bar N, Diels J, van Sanden S, Mendes J, Lee S, Hernando T, Lendvai N, Patel N, Ishida T, Er J, Harrison SJ. Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma with 2-4 Prior Lines of Therapy: Updated Matching-Adjusted Indirect Comparison. Adv Ther. 2026 Feb 2. doi: 10.1007/s12325-025-03479-y. Online ahead of print.

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• Jagannath S, Martin TG, Lin Y, Cohen AD, Raje N, Htut M, Deol A, Agha M, Berdeja JG, Lesokhin AM, Liegel JJ, Rossi A, Lieberman-Cribbin A, Usmani SZ, Dhakal B, Parekh S, Li H, Wang F, Montes de Oca R, Plaks V, Sun H, Banerjee A, Schecter JM, Lendvai N, Madduri D, Lengil T, Zhu J, Koneru M, Akram M, Patel N, Costa Filho O, Jakubowiak AJ, Voorhees PM. Long-Term (>/=5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma. J Clin Oncol. 2025 Sep;43(25):2766-2771. doi: 10.1200/JCO-25-00760. Epub 2025 Jun 3.

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• Palmer S, Lin Y, Martin TG, Jagannath S, Jakubowiak A, Usmani SZ, Buyukkaramikli N, Phelps H, Slowik R, Pan F, Valluri S, Pacaud L, Jackson G. Extrapolation of Survival Data Using a Bayesian Approach: A Case Study Leveraging External Data from Cilta-Cel Therapy in Multiple Myeloma. Oncol Ther. 2023 Sep;11(3):313-326. doi: 10.1007/s40487-023-00230-x. Epub 2023 Jun 4.

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• Raghunandan S, Pauly M, Blum WG, Qayed M, Dhodapkar MV, Elkhalifa M, Watkins B, Schoettler M, Horwitz E, Parikh S, Chandrakasan S, Leung K, Bryson E, Deeb L, Kaufman JL, Worthington-White D, Alazraki A, Schecter JM, Madduri D, Jackson CC, Zudaire E, Taraseviciute-Morris A, Babich A, Nesheiwat T, Vogel M, Lendvai N, Pacaud L, Williams KM. BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma. J Immunother Cancer. 2023 May;11(5):e006684. doi: 10.1136/jitc-2023-006684.

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• Mateos MV, Weisel K, Martin T, Berdeja JG, Jakubowiak A, Stewart AK, Jagannath S, Lin Y, Diels J, Ghilotti F, Thilakarathne P, Perualila NJ, Cabrieto J, Haefliger B, Erler-Yates N, Hague C, Jackson CC, Schecter JM, Strulev V, Nesheiwat T, Pacaud L, Einsele H, Moreau P. Adjusted comparison of outcomes between patients from CARTITUDE-1 versus multiple myeloma patients with prior exposure to proteasome inhibitors, immunomodulatory drugs and anti-CD38 antibody from the prospective, multinational LocoMMotion study of real-world clinical practice. Haematologica. 2023 Aug 1;108(8):2192-2204. doi: 10.3324/haematol.2022.280482.

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MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Vice President Research and Development, Cellular Therapy
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 25, 2018
• First Posted: June 7, 2018
• Study Start: June 29, 2018
• Primary Completion: August 23, 2022
• Study Completion: August 23, 2022
• Last Updated: July 30, 2025
• Results First Posted: April 2, 2024

Record last verified: 2025-07

Locations

US (17); JP (4)