A Phase 3 Randomized Study Comparing Talquetamab SC in Combination With Daratumumab SC and Pomalidomide (Tal-DP) or Talquetamab SC in Combination With Daratumumab SC (Tal-D) Versus Daratumumab SC, Pomalidomide and Dexamethasone (DPd), in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received at Least 1 Prior Line of Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 864
- 试验地点
- 217
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of the study is to compare the efficacy of talquetamab subcutaneous(ly) (SC) in combination with daratumumab SC and pomalidomide (Tal-DP) and talquetamab SC in combination with daratumumab SC (Tal-D), respectively, with daratumumab SC in combination with pomalidomide and dexamethasone (DPd).
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: a) Multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria and b) Measurable disease at screening as defined by any of the following: i) Serum M-protein level greater than or equal to (>=) 0.5 grams per deciliter (g/dL) (central laboratory); ii) Urine M-protein level >= 200 milligram (mg) per 24 hours (central laboratory); iii) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain >= 10 milligram per deciliter (mg/dL) (central laboratory), and abnormal serum immunoglobulin kappa lambda free light chain ratio
- •Relapsed or refractory disease as defined by: i) Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease by IMWG criteria greater than (>) 60 days after cessation of treatment; ii) Refractory disease is defined as less than (<) 25 percent (%) reduction in monoclonal paraprotein (M-protein) or confirmed progressive disease by IMWG criteria during previous treatment or less than or equal to (<=) 60 days after cessation of treatment
- •Received at least 1 prior line of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide. Participants who have received only 1 prior line of antimyeloma therapy must be considered lenalidomide-refractory (that is, have demonstrated progressive disease by IMWG criteria on or within 60 days of completion of lenalidomide-containing regimen). Participants who have received >=2 prior lines of antimyeloma therapy must be considered lenalidomide exposed
- •Documented evidence of progressive disease based on investigator's determination of response by the 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 immediately prior to the start of administration of study treatment
排除标准
- •Contraindications or life-threatening allergies, hypersensitivity, or intolerance to study drug excipients
- •Disease is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody as defined per IMWG consensus guidelines (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody)
- •Received prior pomalidomide therapy
- •A maximum cumulative dose of corticosteroids to >=140 milligrams (mg) of prednisone or equivalent within 14-day period before the first dose of study drug
- •Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required
- •Plasma cell leukemia (per IMWG criteria) at the time of screening, Waldenström's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS syndrome), or primary amyloid light chain amyloidosis
研究组 & 干预措施
Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and Pomalidomide (Tal-DP)
Participants will receive talquetamab and daratumumab as SC injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug Access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Daratumumab (Drug)
Arm C: Talquetamab SC in Combination With Daratumumab SC (Tal-D)
Participants will receive talquetamab and daratumumab as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Daratumumab (Drug)
Arm B: Daratumumab in Combination With Pomalidomide and Dexamethasone (DPd)
Participants will receive daratumumab as SC injection; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Daratumumab (Drug)
Arm B: Daratumumab in Combination With Pomalidomide and Dexamethasone (DPd)
Participants will receive daratumumab as SC injection; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Pomalidomide (Drug)
Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and Pomalidomide (Tal-DP)
Participants will receive talquetamab and daratumumab as SC injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug Access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Pomalidomide (Drug)
Arm B: Daratumumab in Combination With Pomalidomide and Dexamethasone (DPd)
Participants will receive daratumumab as SC injection; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Dexamethasone (Drug)
Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and Pomalidomide (Tal-DP)
Participants will receive talquetamab and daratumumab as SC injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug Access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Talquetamab (Drug)
Arm A: Talquetamab Subcutaneous (SC) in Combination With Daratumumab SC and Pomalidomide (Tal-DP)
Participants will receive talquetamab and daratumumab as SC injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug Access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Dexamethasone (Drug)
Arm C: Talquetamab SC in Combination With Daratumumab SC (Tal-D)
Participants will receive talquetamab and daratumumab as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Dexamethasone (Drug)
Arm C: Talquetamab SC in Combination With Daratumumab SC (Tal-D)
Participants will receive talquetamab and daratumumab as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug. Upon sponsor notification, participants will enter the Long-Term Extension (LTE) Phase or Drug-access Long-term Extension (DA-LTE) Phase and will continue to receive study treatment until disease progression, unacceptable toxicity, withdrawal of consent or any other criteria specified is fulfilled.
干预措施: Talquetamab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to 6 years 6 months
PFS is defined as time from the date of randomization to the first documentation of disease progression, or death due to any cause, whichever is reported first.
次要结局
- Overall Survival (OS)(Up to 6 years 6 months)
- Overall Response (Partial Response [PR] or Better)(Up to 6 years 6 months)
- Very Good Partial Response (VGPR) or Better Rate(Up to 6 years 6 months)
- Complete Response (CR) or Better Rate(Up to 6 years 6 months)
- Overall Minimal Residual Disease (MRD) Negative CR(Up to 6 years 6 months)
- Progression-free Survival on Next-line Therapy (PFS2)(Up to 6 years 6 months)
- Time to Next Therapy (TTNT)(Up to 6 years 6 months)
- Number of Participants with Adverse Events (AEs)(Up to 6 years 6 months)
- Number of Participants with AEs by Severity(Up to 6 years 6 months)
- Serum Concentrations of Talquetamab(Up to 6 years 6 months)
- Serum Concentrations of Daratumumab(Up to 6 years 6 months)
- Number of Participants with Presence of Anti-Drug Antibodies (ADAs) to Talquetamab(Up to 6 years 6 months)
- Number of Participants With Presence of Anti-Drug Antibodies (ADAs) to Daratumumab(Up to 6 years 6 months)
- Time to Worsening in Symptoms, Functioning, and Overall Health-Related Quality of Life (HRQoL) as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)(Up to 6 years 6 months)
- Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by PROMIS Short Form Version 2.0 -Physical Functioning 8c(Up to 6 years 6 months)
- Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by EORTC-QLQ-C30(Up to 6 years 6 months)
- Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by PRO-CTCAE(Up to 6 years 6 months)
- Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)(Up to 6 years 6 months)
- Time to Worsening in Symptoms, Functioning, and HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)(Up to 6 years 6 months)
- Change From Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q)(Baseline up to 6 years 6 months)
- Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by PROMIS Short Form Version 2.0 -Physical Functioning 8c(Baseline up to 6 years 6 months)
- Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by EORTC-QLQ-C30(Baseline up to 6 years 6 months)
- Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by PRO-CTCAE(Baseline up to 6 years 6 months)
- Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)(Baseline up to 6 years 6 months)
- Change from Baseline in Symptoms, Functioning, and HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)(Baseline up to 6 years 6 months)