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 (CARTITUDE-2)

• ClinicalTrials.gov Identifier: NCT04133636
• Recruitment Status: Active, not recruiting
• First Posted: October 21, 2019
• Last Update Posted: May 31, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: October 18, 2019
• First Posted Date: October 21, 2019
• Last Update Posted Date: May 31, 2023
• Actual Study Start Date: November 7, 2019
• Estimated Primary Completion Date: May 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 18, 2019)

Percentage of Participants with Negative Minimal Residual Disease (MRD) [ Time Frame: At least 1 year after JNJ-68284528 infusion on Day 1 ]

MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate as defined by the International Myeloma Working Group (IMWG) criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 21, 2021)

• Overall Response Rate (ORR) [ Time Frame: Up to 2 years and 6 months ]
  ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
• VGPR or Better Rate [ Time Frame: Up to 2 years and 6 months ]
  The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment.
• Clinical Benefit Rate (CBR) [ Time Frame: Up to 2 years and 6 months ]
  CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.
• Duration of Response (DOR) [ Time Frame: Up to 2 years and 6 months ]
  DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria.
• Time to Response (TTR) [ Time Frame: Up to 2 years and 6 months ]
  TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.
• MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) [ Time Frame: 12 months ]
  MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528.
• Time to MRD Negativity [ Time Frame: Up to 2 years and 6 months ]
  Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status.
• Duration of MRD Negativity [ Time Frame: Up to 2 years and 6 months ]
  Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5).
• MRD Negative Rate Across Clinical Response [ Time Frame: Up to 2 years and 6 months ]
  MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint.
• Number of Participants with Adverse Events by Severity [ Time Frame: Up to 2 years and 6 months ]
  An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.
• Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years and 6 months ]
  An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Number of Participants with Laboratory Abnormalities [ Time Frame: Up to 2 years and 6 months ]
  Number of participants with laboratory abnormalities will be reported.
• Number of Participants with Vital Sign Abnormalities [ Time Frame: Up to 2 years and 6 months ]
  Number of participants with vital sign abnormalities will be reported.
• Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [ Time Frame: Up to 1 year ]
  Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported.
• Systemic Inflammatory Cytokine Concentrations [ Time Frame: Up to 1 year ]
  Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.
• Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [ Time Frame: Up to 1 year ]
  Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
• Number of Participants with Anti-JNJ-68284528 Antibodies [ Time Frame: Up to 1 year ]
  Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.

Original Secondary Outcome Measures (submitted: October 18, 2019)

• MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) [ Time Frame: 12 months ]
  MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528.
• Time to MRD Negativity [ Time Frame: Up to 2 years ]
  Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status.
• Duration of MRD Negativity [ Time Frame: Up to 2 years ]
  Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5).
• MRD Negative Rate Across Clinical Response [ Time Frame: Up to 2 years ]
  MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint.
• Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
  ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
• VGPR or Better Rate [ Time Frame: Up to 2 years ]
  The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment.
• Clinical Benefit Rate (CBR) [ Time Frame: Up to 2 years ]
  CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.
• Duration of Response (DOR) [ Time Frame: Up to 2 years ]
  DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria.
• Time to Response (TTR) [ Time Frame: Up to 2 years ]
  TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.
• Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years ]
  An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
• Number of Participants with Adverse Events by Severity [ Time Frame: Up to 2 years ]
  An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.
• Maximum Blood Concentration (Cmax) of JNJ-68284528 [ Time Frame: Up to 1 year ]
  Cmax is defined as the maximum observed blood concentration.
• Time to Reach Maximum Observed Blood Concentration (Tmax) of JNJ-68284528 [ Time Frame: Up to 1 year ]
  Tmax is defined as actual sampling time to reach maximum observed blood concentration.
• Time to Last Quantifiable Blood Concentration (Tlast) of JNJ-68284528 [ Time Frame: Up to 1 year ]
  Tlast is defined as the time to last observed quantifiable blood concentration.
• Area Under the Blood Concentration-Time Curve from Time Zero to Last Quantifiable Time (AUClast) of JNJ-68284528 [ Time Frame: Up to 1 year ]
  The AUClast is the area under the blood concentration-time curve from time zero to last quantifiable time.
• Area Under the Blood Concentration-Time Curve from Time Zero to Infinite Time (AUCinfinity) of JNJ-68284528 [ Time Frame: Up to 1 year ]
  AUCinfinity is defined as area under the blood analyte concentration-time curve from time 0 to infinite time of JNJ-68284528.
• Rate Constant (Lambda[z]) [ Time Frame: Up to 1 year ]
  Lambda(z) is the first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
• Elimination Half-Life (t1/2) of JNJ-68284528 [ Time Frame: Up to 1 year ]
  t1/2 is defined as the time measured for the blood concentration to decrease by 1 half of its original concentration.
• Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [ Time Frame: Up to 2 years ]
  Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported.
• Systemic Inflammatory Cytokine Concentrations [ Time Frame: Up to 2 years ]
  Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.
• Levels of CAR-T Cell Activation Markers [ Time Frame: Up to 2 years ]
  CAR-T cell activation markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry or cytometry by time of flight (CyTOF) or both and correlated with response.
• Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [ Time Frame: Up to 2 years ]
  Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
• Number of Participants with Anti-JNJ-68284528 Antibodies [ Time Frame: Up to 2 years ]
  Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma
• Brief Summary: The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: JNJ-68284528
  Participants in cohort A,B,C, D, E and F will receive JNJ-68284528 intravenously.
  Other Name: Ciltacabtagene autoleucel (cilta-cel)
• Drug: Lenalidomide
  Some participants in cohort D and all participants in cohort E will also receive lenalidomide capsules orally.
• Drug: Daratumumab
  Participants in cohort E will also receive daratumumab subcutaneous (SC) injection.
• Drug: Bortezomib
  Participants in cohort E will also receive bortezomib subcutaneously.
• Drug: Dexamethasone
  Participants in cohort E will also receive dexamethasone orally or intravenously.

Study Arms

Experimental: JNJ-68284528

Single group assignment-After lymphodepletion, JNJ-68284528 will be administered as single infusion to participants in cohort A (Progressive disease after 1-3 prior lines of therapy), cohort B (Early relapse after front-line), cohort C (Relapsed/refractory multiple myeloma after PI, IMiD, anti-CD38, and anti- BCMA therapy), cohort D (Less than CR after ASCT front-line therapy; some participants will be administered JNJ-68284528 followed by lenalidomide), cohort F (Newly diagnosed multiple myeloma [NDMM] with standard risk [international staging system {ISS} Stage I and II] and after initiation of therapy). Participants in cohort E (NDMM, transplant not planned, high risk disease) will first be administered with quadruplet induction regimen of daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd), followed by lymphodepletion and JNJ-68284528, followed by consolidation regimen of lenalidomide.

Interventions:

• Drug: JNJ-68284528
• Drug: Lenalidomide
• Drug: Daratumumab
• Drug: Bortezomib
• Drug: Dexamethasone

• Publications *: Cohen AD, Mateos MV, Cohen YC, Rodriguez-Otero P, Paiva B, van de Donk NWCJ, Martin T, Suvannasankha A, De Braganca KC, Corsale C, Schecter JM, Varsos H, Deraedt W, Wang L, Vogel M, Roccia T, Xu X, Mistry P, Zudaire E, Akram M, Nesheiwat T, Pacaud L, Avivi I, San-Miguel J. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023 Jan 19;141(3):219-230. doi: 10.1182/blood.2022015526.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 30, 2023): 169
• Original Estimated Enrollment (submitted: October 18, 2019): 40
• Estimated Study Completion Date: May 30, 2025
• Estimated Primary Completion Date: May 30, 2025 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany, Israel, Netherlands, Saudi Arabia, Spain, United States
• Removed Location Countries: Singapore

Administrative Information

• NCT Number: NCT04133636
• Other Study ID Numbers: CR108581; 2018-004124-10 ( EudraCT Number ); 68284528MMY2003 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: May 2023