A Phase 3 Randomized Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Monoclonal Antibody and Lenalidomide
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 614
- 试验地点
- 359
- 主要终点
- Part 1: Progression-free Survival (PFS)
研究概览
简要总结
The purpose of this study is to compare the efficacy of teclistamab with PVd/Kd in Part 1 and to further characterize safety and efficacy of an alternative dosing for teclistamab in Part 2 in participants with relapsed or refractory multiple myeloma.
详细描述
Multiple myeloma is an incurable, malignant, plasma cell disorder. Teclistamab (JNJ-64007957) is a full-size, Immunoglobulin G (IgG) 4 proline, alanine, and alanine (PAA) bispecific antibody that targets the cluster of differentiation (CD3) receptor expressed on the surface of T cells and B cell maturation antigen (BCMA). With its dual binding sites, teclistamab is able to draw CD3 positive T cells in close proximity to BCMA positive cells, resulting in T-cell activation and subsequent lysis of BCMA positive cells. Pomalidomide is a third-generation immunomodulatory imide drug (IMiD) that exerts potent, direct tumoricidal and immune-enhancing effects and Carfilzomib is a second-generation proteasome inhibitor that inhibits proteasome which results in disruption of protein turnover and induces apoptosis. The primary hypothesis of this study is that teclistamab monotherapy (Arm A) will significantly improve progression free survival (PFS) compared with investigator's choice of PVd or Kd (Arm B) in participants with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. The study will include a screening phase, treatment phase, and follow-up phase. Safety will be assessed by physical examinations, neurologic examinations, eastern cooperative oncology group (ECOG) performance status, clinical laboratory tests, vital signs, and AE monitoring. The overall duration of the study will be up to 9 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of multiple myeloma as defined by the criteria below: (a)Multiple myeloma diagnosis according to International Myeloma Working Group (IMWG) diagnostic criteria (b) Measurable disease at screening as defined by any of the following: (1) Serum M-protein level greater than or equal to (>=)0.5 grams per deciliter (g/dL) (central laboratory); or (2) Urine M-protein level >=200 milligrams (mg)/24 hours (central laboratory); or (3) Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti- cluster of differentiation 38 (CD38) monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line
- •Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator's determination of response by International myeloma working group (IMWG) criteria
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
- •A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
- •Must be willing and able to adhere to the lifestyle restrictions specified in this protocol
排除标准
- •Received any prior B cell maturation antigen (BCMA)-directed therapy
- •A participant is not eligible to receive PVd as control therapy if any of the following are present: (1) Received prior pomalidomide therapy, (2) Does not meet criteria for bortezomib retreatment (3) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib, (4) Grade 1 peripheral neuropathy with pain or Grade greater than or equal to (>=) 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, (5) Received a strong cytochrome P (CYP) 3A4 inducer within 5 half-lives prior to randomization; A participant is not eligible to receive Kd as control therapy if any of the following are present:(1) Received prior carfilzomib therapy, (2) Uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic blood pressure >99 mmHg despite optimal treatment (3) Grade 2 peripheral neuropathy with pain or Grade >=3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0, (4) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any adverse event [AE] related to carfilzomib)
- •Received a maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14 days prior to randomization
- •Received a live, attenuated vaccine within 4 weeks before randomization
- •Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma
- •Plasma cell leukemia at the time of screening, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein (POEMS) syndrome and skin changes, or primary amyloid light chain amyloidosis
研究组 & 干预措施
Teclistamab
Participants will receive teclistamab monotherapy in Part 1 and an alternative dosing regimen of teclistamab in Part 2.
干预措施: Teclistamab (Drug)
Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)
Participants will receive either PVd or Kd based on principal investigator's choice during Part 1 of the study.
干预措施: Bortezomib (Drug)
Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)
Participants will receive either PVd or Kd based on principal investigator's choice during Part 1 of the study.
干预措施: Carfilzomib (Drug)
Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)
Participants will receive either PVd or Kd based on principal investigator's choice during Part 1 of the study.
干预措施: Pomalidomide (Drug)
Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)
Participants will receive either PVd or Kd based on principal investigator's choice during Part 1 of the study.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Part 1: Progression-free Survival (PFS)
时间窗: Up to 9 years
PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the International myeloma working group (IMWG) 2016 response criteria, or death due to any cause, whichever occurs first.
Part 2: Number of Participants Reporting Cytokine Release Syndrome (CRS) Cases by Severity
时间窗: Up to 9 years
Severity for CRS will be graded as follows: Grade 1: Fever (Temperature greater than or equal to \[\>=\] 38°C); Grade 2: Fever (Temperature \>=38°C) with either: hypotension and/or hypoxia requiring low-flow nasal cannula or blow-by; Grade 3: Fever (Temperature \>=38°C) with either: hypotension and/or hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask; Grade 4: Fever (Temperature \>=38°C) with either: hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring positive pressure and Grade 5: Death.
次要结局
- Part 1 and 2: Complete Response (CR) or Better Response(Up to 9 years)
- Part 1 and 2: Overall Response (Partial Response [PR] or Better)(Up to 9 years)
- Part 1 and 2: Very Good Partial Response (VGPR) or Better Response(Up to 9 years)
- Part 1: Duration of Response (DOR)(Up to 9 years)
- Part 1: Time to Next Treatment (TTNT)(Up to 9 years)
- Part 1: Progression-free Survival on Next-line Therapy (PFS2)(Up to 9 years)
- Part 1: Overall Survival (OS)(Up to 9 years)
- Part 1 and 2: Number of Participants with Adverse Events (AEs) by Severity(Up to 9 years)
- Part 1 and 2: Number of Participants with Serious Adverse Events (SAEs) by Severity(Up to 9 years)
- Part 1 and 2: Number of Participants with Abnormal Laboratory Results(Up to 9 years)
- Part 1 and 2: Serum Concentrations of Teclistamab(Up to 9 years)
- Part 1 and 2: Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab(Up to 9 years)
- Part 1: Change from Baseline in Symptoms, Functioning, and Overall Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30)(Baseline up to 9 years)
- Part 1: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score(Baseline up to 9 years)
- Part 1: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Baseline up to 9 years)
- Part 1: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)(Baseline up to 9 years)
- Part 1: Time to Worsening in Symptoms, Functioning, and Overall HRQoL(Up to 9 years)
- Part 1: PFS in Participants in High-risk Molecular Features(Up to 9 years)
- Part 1: Depth of Response in Participants in High-risk Molecular Features(Up to 9 years)