Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04923893 | A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy | PHASE3 | ACTIVE NOT_RECRUITING | 743 | — | — | Aug 19, 2021 | Sep 22, 2036 | Jun 5, 2026 | 136 | United States, Argentina +24 |
| NCT04181827 | A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma | PHASE3 | ACTIVE NOT_RECRUITING | 419 | — | — | Jun 12, 2020 | Apr 9, 2029 | May 11, 2026 | 88 | United States, Australia +14 |
| NCT07149857 | A Study to Evaluate Efficacy and Safety of Ciltacabtagene Autoleucel | PHASE2 | RECRUITING | 60 | — | — | Oct 3, 2025 | Apr 6, 2029 | Jun 5, 2026 | 17 | United States, Australia +1 |
| NCT06550895 | A Study of Ciltacabtagene Autoleucel and Talquetamab for the Treatment of Participants With High-Risk Multiple Myeloma | PHASE2 | ACTIVE NOT_RECRUITING | 11 | — | — | Sep 16, 2024 | Aug 26, 2027 | Jun 5, 2026 | 9 | United States, Australia |
| NCT06577025 | A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma | PHASE2 | ACTIVE NOT_RECRUITING | 43 | — | — | Aug 20, 2024 | Sep 30, 2030 | Jun 5, 2026 | 16 | United States, Australia +3 |
| NCT05347485 | A Study of JNJ-68284528 Out-of-Specification (OOS) for Commercial Release in Participants With Multiple Myeloma | PHASE2 | COMPLETED | 86 | — | — | May 13, 2022 | Dec 15, 2023 | Apr 25, 2025 | 18 | United States |
Progression-free survival is defined as the time from the date of randomization to the date of first documented Progressive Disease (PD), as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.
Participants in CR or better who achieve MRD-negative status at 12 months after cilta-cel infusion with a sensitivity of 10\^-5, prior to progressive disease (PD) or subsequent anti-myeloma therapy will be reported.
An AE is any untoward medical occurrence in a participant administered a pharmaceutical (investigational or non-investigational) product. It does not necessarily have a causal relationship with the investigational product. The severity of AEs has 5 grades based on NCI-CTCAE version 5.0 criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; Grade 5: Death.
Rate of Response with curative potential is defined as the percentage of participants with a composite of durable (at least 2 years) minimal residual disease (MRD) (10\^-5) negativity with complete response/stringent complete response (CR/sCR) by serology and negative positron emission tomography/computed tomography (PET/CT) imaging at 5-years after start of induction therapy. This includes: negative imaging at 5-year landmark time; MRD-negative status (at 10\^-5) in 2 bone marrow examinations that are a minimum of 2 years apart; response of CR or better per the International Myeloma Working Group (IMWG) criteria; no examination showing MRD-positive status or relapse from CR in between assessments.
PFS is defined as the time from the date of randomization to either progressive disease (PD), according to the IMWG response criteria, or death, whichever occurs first.
PFS is defined as the time from the date of randomization to either PD, according to the IMWG response criteria, or death, whichever occurs first.
ORR is defined as the percentage of participants who had partial response (PR) or better (sCR+CR+VGPR+PR) according to the International Myeloma Working Group (IMWG) response criteria, as assessed by the investigator. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (\<) 5 percentage (%) plasma cells (PCs) in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (\>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>= 90 percentage (%) or to \<200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hour.
| Arm | Type | Description |
|---|---|---|
| Arm A: VRd+Rd (Standard Therapy) | EXPERIMENTAL | Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m\^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity. |
| Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) | EXPERIMENTAL | Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg). |
| Arm A: PVd or DPd (Standard Therapy) | EXPERIMENTAL | Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier. |
| Arm B: (Ciltacabtagene Autoleucel [Cilta-cel]) | EXPERIMENTAL | Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of cilta-cel along with conditioning regimen (cyclophosphamide 300 milligram \[mg\]/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily, for 3 days), and cilta-cel infusion 0.75 \* 10\^6 chimeric antigen receptor (CAR)-positive viable T cells/ kilogram (kg). |
| Cohort A | EXPERIMENTAL | Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide daily for 3 days, followed by cilta-cel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion. |
| Cohort B | EXPERIMENTAL | Participants will undergo apheresis and continue to receive 1-2 more cycles of the induction regimen (DRd, VRd or DVRd regimen, in accordance with institution standard of care, and is not considered study treatment) that they were receiving prior to screening. After completion of induction therapy, participants will receive a conditioning regimen of cyclophosphamide and fludarabine daily for 3 days, followed by Ciltacel IV infusion on Day 1. Participants will later enter the post-treatment phase, which will start on Day 113 and last until end of study or cohort completion. |
| Cohort 1:Cilta-cel + Talquetamab Consolidation Post Chimeric Antigen Receptor T cell (CAR-T) Therapy | EXPERIMENTAL | Participants with relapsed and/or refractory multiple myeloma (RRMM) will be administered Cilta-cel followed by multiple cycles of talquetamab consolidation treatment and will be followed up until death, lost to follow-up, consent withdrawal, or study end, whichever occurs first. |
| Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel | EXPERIMENTAL | Participants will undergo apheresis followed by 4 cycles of DVRd induction (each cycle is of 28 days) and cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release, and completion of induction, participants will begin consolidation with 4 cycles of Tal-D (each cycle is of 28 days), followed by a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days); cilta-cel will be administered 5 to 7 days after the start of the conditioning regimen. |
| Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation | EXPERIMENTAL | Participants will undergo apheresis followed by 4 cycles of DVRd induction and Cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release and completion of induction, participants will begin consolidation with a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days) with infusion of cilta-cel 5 to 7 days after the start of the conditioning regimen. Following cilta-cel infusion, alternating cycles of Tal-D (Cycle 1, 3, 5, and 7) and Tec-D (Cycle 2, 4, 6, and 8) will be started, no earlier than Day 84 and no later than Day 168 post cilta-cel infusion. Each cycle of Tal-D or Tec-D is 84 days which includes an extended treatment-free interval. |
| Ciltacabtagene Autoleucel (Cilta-cel) | EXPERIMENTAL | Eligible participants will receive bridging therapy (that is, anti-plasma cell directed treatment) based on participant's clinical status and timing of availability of cilta-cel (JNJ-68284528) along with lymphodepleting chemotherapy (cyclophosphamide 300 milligrams per meter square \[mg/m\^2\] intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily, for 3 days). After 5 to 7 days of initiating lymphodepleting chemotherapy, participants will receive a single IV infusion of cilta-cel (JNJ-68284528) at a total targeted dose of 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells per kilogram (cells/kg). |
| Name | Type | Description |
|---|---|---|
| Bortezomib | DRUG | Bortezomib will be administered SC. |
| Dexamethasone | DRUG | Dexamethasone will be administered orally. |
| Lenalidomide | DRUG | Lenalidomide will be administered orally. |
| Cilta-cel | DRUG | Cilta-cel infusion will be administered. |
| Cyclophosphamide | DRUG | Cyclophosphamide will be administered intravenously. |
| Fludarabine | DRUG | Fludarabine will be administered intravenously. |
| Pomalidomide | DRUG | Pomalidomide 4 mg will be administered orally. |
| Daratumumab | DRUG | Daratumumab 1800 mg will be administered SC. |
| Induction therapy | DRUG | Induction therapy consist of bortezomib, lenalidomide, and dexamethasone (VRd) or daratumumab, lenalidomide, and dexamethasone (DRd) or daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd), will will be administered. |
| Talquetamab | DRUG | Talquetamab will be administered subcutaneously. |
| Teclistamab | DRUG | Teclistamab will be administered subcutaneously. |
| Lymphodepleting Therapy (Cyclophosphamide and Fludarabine) | DRUG | Lymphodepleting therapy (cyclophosphamide and fludarabine) will be administered intravenously. |
Inclusion Criteria: * Documented diagnosis of multiple myeloma (MM) according to International Myeloma Working Group (IMWG) diagnostic criteria * Measurable disease at screening as defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=)1.0 gram...