A Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 587
- 试验地点
- 341
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to compare the efficacy of teclistamab daratumumab (Tec-Dara) with daratumumab subcutaneously (SC) in combination with pomalidomide and dexamethasone (DPd) or daratumumab SC in combination with bortezomib and dexamethasone (DVd).
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 multiple myeloma as defined by the criteria: a. multiple myeloma diagnosis according to the 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 gram per deciliter (g/dL); or 2) urine M-protein level >=200 milligrams (mg)/24 hours; or 3) serum immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Received 1 to 3 prior line(s) of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide; a. participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory. Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion
- •Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen
- •Have an eastern cooperative oncology group (ECOG) performance status score of 0, 1, or 2 at screening and prior to the start of administration of study treatment
- •Have clinical laboratory values within the specified range
排除标准
- •Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients. Additional exclusion criteria pertaining to specific study drugs include:
- •A participant is not eligible to receive daratumumab subcutaneous (SC) in combination with pomalidomide and dexamethasone (DPd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide, 2) Disease that is considered refractory to pomalidomide per IMWG,
- •A participant is not eligible to receive daratumumab SC in combination with bortezomib and dexamethasone (DVd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib, 2) Grade 1 peripheral neuropathy with pain or Grade >= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, 3) Disease that is considered refractory to bortezomib per IMWG, 4) Received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization
- •Received any prior B cell maturation antigen (BCMA)-directed therapy
- •Has disease that is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody per IMWG
- •Received a cumulative dose of corticosteroids equivalent to >=140 mg of prednisone within 14 days before randomization
- •Received a live, attenuated vaccine within 4 weeks before randomization
- •Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis
研究组 & 干预措施
Arm A: Teclistamab-daratumumab (Tec-Dara)
Participants will receive teclistamab and daratumumab by subcutaneous (SC) injection. Step-up doses of teclistamab will be given prior to the first full dose. Participants who are still receiving the treatment and benefiting from it may enter the long-term extension (LTE) and drug access (DA)-LTE Phases to continue their current treatment until end of the study.
干预措施: Teclistamab (Drug)
Arm B: DPd or DVd
Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Participants randomized to Arm B who do not cross over to Tec-Dara may continue DPd/DVd treatment during the LTE phase. Following the completion of LTE phase, participants who crossed over to Tec-Dara during the LTE may enter the DA LTE and continue to receive study treatment with Tec Dara. Any participants still receiving DPd/DVd at the end of the LTE may not cross over to Tec-Dara and will not continue into the DA-LTE.
干预措施: Daratumumab (Drug)
Arm A: Teclistamab-daratumumab (Tec-Dara)
Participants will receive teclistamab and daratumumab by subcutaneous (SC) injection. Step-up doses of teclistamab will be given prior to the first full dose. Participants who are still receiving the treatment and benefiting from it may enter the long-term extension (LTE) and drug access (DA)-LTE Phases to continue their current treatment until end of the study.
干预措施: Daratumumab (Drug)
Arm B: DPd or DVd
Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Participants randomized to Arm B who do not cross over to Tec-Dara may continue DPd/DVd treatment during the LTE phase. Following the completion of LTE phase, participants who crossed over to Tec-Dara during the LTE may enter the DA LTE and continue to receive study treatment with Tec Dara. Any participants still receiving DPd/DVd at the end of the LTE may not cross over to Tec-Dara and will not continue into the DA-LTE.
干预措施: Bortezomib (Drug)
Arm B: DPd or DVd
Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Participants randomized to Arm B who do not cross over to Tec-Dara may continue DPd/DVd treatment during the LTE phase. Following the completion of LTE phase, participants who crossed over to Tec-Dara during the LTE may enter the DA LTE and continue to receive study treatment with Tec Dara. Any participants still receiving DPd/DVd at the end of the LTE may not cross over to Tec-Dara and will not continue into the DA-LTE.
干预措施: Dexamethasone (Drug)
Arm B: DPd or DVd
Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously. Participants randomized to Arm B who do not cross over to Tec-Dara may continue DPd/DVd treatment during the LTE phase. Following the completion of LTE phase, participants who crossed over to Tec-Dara during the LTE may enter the DA LTE and continue to receive study treatment with Tec Dara. Any participants still receiving DPd/DVd at the end of the LTE may not cross over to Tec-Dara and will not continue into the DA-LTE.
干预措施: Pomalidomide (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Up to 5 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) criteria, or death due to any cause, whichever occurs first.
次要结局
- Overall Response (Partial Response [PR] or Better)(Up to 5 years)
- Very Good Partial Response (VGPR) or Better(Up to 5 years)
- Complete Response (CR) or Better(Up to 5 years)
- Minimal Residual Disease (MRD)-negativity(Up to 5 years)
- Progression Free Survival on Next-line Therapy (PFS2)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- Time to Next Treatment (TTNT)(Up to 5 years)
- Duration of Response(Up to 5 years)
- Number of Participants with Adverse Events (AEs) by Severity(Up to 5 years)
- Serum Concentration of Teclistamab(Up to 5 years)
- Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Daratumumab(Up to 5 years)
- Time to Worsening of Symptoms(Up to 5 years)
- 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 5 years)
- 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 5 years)
- Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form v2.0 - Physical Function 8c (PROMIS PF 8c)(Baseline up to 5 years)
- 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 6 months)
- Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)(Baseline up to 5 years)
- Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)(Baseline up to 5 years)
- PFS in Participants with High-risk Molecular Features(Up to 5 years)
- Depth of Response in Participants in High-risk Molecular Features(Up to 5 years)