Phase 2/3, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Subjects With Newly Diagnosed Multiple Myeloma Not Eligible for Transplant
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 660
- 试验地点
- 49
- 主要终点
- Phase 2 and 3: Percentage of Participants with Adverse Events (AE)s
研究概览
简要总结
Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. This is a study to determine the adverse events, change in disease activity, and pharmacokinetics of Etentamig in adult participants with MM.
Etentamig is an investigational drug being developed for the treatment of MM. This study is broken into 2 phases; phase 2 with 3 study arms and phase 3 with 2 study arms. Participants in phase 2 will receive 1 of 3 doses of etentamig in combination with daratumumab. Participants in phase 3 will receive etentamig at RP3D in combination with daratumumab, or daratumumab, lenalidomide, and dexamethasone (DRd). Around 660 adult participants with MM will be enrolled at approximately 155 sites worldwide
Participants in phase 2 will receive 1 of 3 doses of etentamig as intravenous (IV) infusions, combination with subcutaneous (SC) injections of daratumumab. Participants in phase 3 will receive RP3D doses of etentamig as IV infusions, combination with SC injections of daratumumab, or SC injections of daratumumab, capsules of lenalidomide, and tablet/ IV injections of dexamethasone (DRd). The study duration is approximately 16 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Participants must have confirmed new diagnosis of multiple myeloma (NDMM) according to the International Myeloma Working Group (IMWG) diagnostic criteria, and per investigator's judgement, participant is not suitable to receive high-dose chemotherapy and stem cell transplantation due to factors likely to have a negative impact on tolerability of high dose chemotherapy and autologous stem cell transplants (ASCT).
- •IMWG Myeloma Frailty Index Score of >= 1
- •All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:
- •Serum M-protein >= 0.5 g/dL (>= 5 g/L).
- •Urine M-protein >= 200 mg/24 hours.
- •Serum free light chain (FLC) >= 100 mg/L (>= 10 mg/dL) (involved light chain) and an abnormal serum kappa lambda ratio only for participants without measurable serum or urine M-protein.
排除标准
- •Prior or current systemic therapy or stem cell transplant (SCT) for multiple myeloma or any plasma cell dyscrasia other than short course of corticosteroids
- •Participant treated with any investigational treatment within 30 days or 5 half-lives of the treatment (whichever is longer) prior to the first dose of study treatment or is currently enrolled in another clinical study
- •Participant who has known active central nervous system involvement of MM.
- •Participant who has history of clinically significant renal, neurologic, psychiatric, endocrine, metabolic, immunologic, pulmonary, or hepatic disease within the last 6 months that, in the investigator's opinion, would adversely affect the participant's participation in the study.
研究组 & 干预措施
Phase 2: Etentamig + Daratumumab Dose A
Participants will receive etentamig dose A in combination with daratumumab until the recommended phase 3 dose (RP3D), as part of the approximately 16 year study duration.
干预措施: Etentamig (Drug)
Phase 3: Etentamig + Daratumumab RP3D
Participants will receive etentamig at the RP3D in combination with daratumumab, as part of the approximately 16 year study duration.
干预措施: Etentamig (Drug)
Phase 2: Etentamig + Daratumumab Dose B
Participants will receive etentamig dose B in combination with daratumumab until the RP3D, as part of the approximately 16 year study duration.
干预措施: Etentamig (Drug)
Phase 2: Etentamig + Daratumumab Dose C
Participants will receive etentamig dose C in combination with daratumumab until the RP3D, as part of the approximately 16 year study duration.
干预措施: Etentamig (Drug)
Phase 3: Daratumumab, Lenalidomide, and Dexamethasone (DRd)
Participants will receive DRd, as part of the approximately 16 year study duration.
干预措施: Lenalidomide (Drug)
Phase 2: Etentamig + Daratumumab Dose B
Participants will receive etentamig dose B in combination with daratumumab until the RP3D, as part of the approximately 16 year study duration.
干预措施: Daratumumab (Drug)
Phase 2: Etentamig + Daratumumab Dose A
Participants will receive etentamig dose A in combination with daratumumab until the recommended phase 3 dose (RP3D), as part of the approximately 16 year study duration.
干预措施: Daratumumab (Drug)
Phase 3: Daratumumab, Lenalidomide, and Dexamethasone (DRd)
Participants will receive DRd, as part of the approximately 16 year study duration.
干预措施: Daratumumab (Drug)
Phase 2: Etentamig + Daratumumab Dose C
Participants will receive etentamig dose C in combination with daratumumab until the RP3D, as part of the approximately 16 year study duration.
干预措施: Daratumumab (Drug)
Phase 3: Daratumumab, Lenalidomide, and Dexamethasone (DRd)
Participants will receive DRd, as part of the approximately 16 year study duration.
干预措施: Dexamethasone (Drug)
Phase 3: Etentamig + Daratumumab RP3D
Participants will receive etentamig at the RP3D in combination with daratumumab, as part of the approximately 16 year study duration.
干预措施: Daratumumab (Drug)
结局指标
主要结局
Phase 2 and 3: Percentage of Participants with Adverse Events (AE)s
时间窗: Up to Approximately 16 Years
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Phase 2: Change in Clinical Activity
时间窗: Up to Approximately 52 weeks
Clinical activity is defined as change in response rates \[Overall Response Rate (ORR), Complete Response (CR) or Better, Very Good Partial Response (VGPR), Partial Response (PR)\] as determined International Myeloma Working Group (IMWG (2016).
Phase 3: Minimal Residual Disease (MRD) Negative CR Rate
时间窗: Up to Approximately 52 weeks
MRDnegCR rate, is defined as the percentage of participants who have achieved stringent complete response (sCR) or CR as assessed by independent review committee (IRC) and have negative MRD defined at 10\^-5 threshold as assessed by next generation sequencing (NGS).
Phase 3: Progression-Free Survival (PFS)
时间窗: Up to Approximately 130 Months
PFS is defined as the duration from the date of randomization to the date of confirmed disease progression (PD) determined by IRC per IMWG (2016) response criteria, or death, whichever occurs first.
Phase 2 and 3: Percentage of Participants with Adverse Events (AE)s
时间窗: Up to Approximately 16 Years
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Phase 2: Change in Clinical Activity
时间窗: Up to Approximately 52 weeks
Clinical activity is defined as change in response rates \[Overall Response Rate (ORR), Complete Response (CR) or Better, Very Good Partial Response (VGPR), Partial Response (PR)\] as determined International Myeloma Working Group (IMWG (2016).
Phase 3: Minimal Residual Disease (MRD) Negative CR Rate
时间窗: Up to Approximately 52 weeks
MRDnegCR rate, is defined as the percentage of participants who have achieved stringent complete response (sCR) or CR as assessed by independent review committee (IRC) and have negative MRD defined at 10\^-5 threshold as assessed by next generation sequencing (NGS).
Phase 3: Progression-Free Survival (PFS)
时间窗: Up to Approximately 130 Months
PFS is defined as the duration from the date of randomization to the date of confirmed disease progression (PD) determined by IRC per IMWG (2016) response criteria, or death, whichever occurs first.
次要结局
- Phase 2: MRD Negative CR Rate(Up to Approximately 52 Weeks)
- Phase 2: Area Under the Serum Concentration-Time Curve (AUC)(Up to Approximately 12 Months)
- Phase 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability(Up to Approximately 16 Years)
- Phase 2: PFS(Up to Approximately 130 Months)
- Phase 2: Sustained MRD Negativity Rate(Up to Approximately 12 Months)
- Phase 2: Overall Survival (OS)(Up to Approximately 16 Years)
- Phase 3: OS(Up to Approximately 16 Years)
- Phase 2: Maximum Observed Serum Concentration (Cmax)(Up to Approximately 12 Months)
- Phase 2: Time to Cmax (Time to Maximum Observed Concentration, Tmax)(Up to Approximately 12 Months)
- Phase 3: Sustained MRD Negativity Rate(Up to Approximately 12 Months)
- Phase 3: Change from Baseline in EORTC QLQ-C30 Global Health Status/QoL Score(Up to Approximately 16 Years)
- Phase 2: Negative ADAs(Up to Approximately 90 days after the last dose of study treatment)
- Phase 2: Positive Anti-Drug Antibodies (ADAs)(Up to Approximately 90 days after the last dose of study treatment)
- Phase 2: Neutralizing Anti-Drug Antibodies (NAbs)(Up to Approximately 90 days after the last dose of study treatment)
- Phase 3: Rate of >= CR(Up to Approximately 12 Months)
- Phase 3: Rate of >= VGPR or Better(Up to Approximately 12 Months)
- Phase 3: ORR(Up to Approximately 52 Weeks)
- Phase 3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability(Up to Approximately 16 Years)
- Phase 3: Time to Response (TTR)(Up to Approximately 12 Months)
- Phase 3: Duration of Response (DOR)(Up to Approximately 16 Years)
- Phase 3: Time-to-Progression (TTP)(Up to Approximately 16 Years)
- Phase 3: Event Free Survival (EFS)(Up to Approximately 16 Years)
- Phase 3: Progression-Free Survival on Subsequent Therapy (PFS2)(Up to Approximately 16 Years)
- Phase 3: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Functioning Score(Up to Approximately 16 Years)
- Phase 3: Change from Baseline and Time to Deterioration in the Remaining Scales and Items of EORTC QLQ-C30(Up to Approximately 16 Years)
- Phase 3: Change from Baseline in European Quality of Life 5 Dimensions (EQ-5D-5L) Scores(Up to Approximately 16 Years)
- Phase 3: Symptomatic AEs as Assessed by the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to Approximately 16 Years)
- Phase 3: Overall Bother Due to Treatment Side Effects as Assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) GP5(Up to Approximately 16 Years)
- Phase 3: Change from Baseline in Patient Global Impression of Severity (PGIS) Scores(Up to Approximately 16 Years)
- Phase 3: Rate of >= CR(Up to Approximately 12 Months)
- Phase 3: Sustained MRD Negativity Rate(Up to Approximately 12 Months)
- Phase 2: Positive Anti-Drug Antibodies (ADAs)(Up to Approximately 90 days after the last dose of study treatment)
- Phase 2: Negative ADAs(Up to Approximately 90 days after the last dose of study treatment)
- Phase 2: Neutralizing Anti-Drug Antibodies (NAbs)(Up to Approximately 90 days after the last dose of study treatment)
- Phase 3: OS(Up to Approximately 16 Years)
- Phase 2: MRD Negative CR Rate(Up to Approximately 52 Weeks)
- Phase 2: PFS(Up to Approximately 130 Months)
- Phase 2: Sustained MRD Negativity Rate(Up to Approximately 12 Months)
- Phase 2: Area Under the Serum Concentration-Time Curve (AUC)(Up to Approximately 12 Months)
- Phase 2: Overall Survival (OS)(Up to Approximately 16 Years)
- Phase 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability(Up to Approximately 16 Years)
- Phase 2: Maximum Observed Serum Concentration (Cmax)(Up to Approximately 12 Months)
- Phase 2: Time to Cmax (Time to Maximum Observed Concentration, Tmax)(Up to Approximately 12 Months)
- Phase 3: Rate of >= VGPR or Better(Up to Approximately 12 Months)
- Phase 3: ORR(Up to Approximately 52 Weeks)
- Phase 3: Time to Response (TTR)(Up to Approximately 12 Months)
- Phase 3: Duration of Response (DOR)(Up to Approximately 16 Years)
- Phase 3: Time-to-Progression (TTP)(Up to Approximately 16 Years)
- Phase 3: Event Free Survival (EFS)(Up to Approximately 16 Years)
- Phase 3: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability(Up to Approximately 16 Years)
- Phase 3: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Physical Functioning Score(Up to Approximately 16 Years)
- Phase 3: Change from Baseline in EORTC QLQ-C30 Global Health Status/QoL Score(Up to Approximately 16 Years)
- Phase 3: Change from Baseline and Time to Deterioration in the Remaining Scales and Items of EORTC QLQ-C30(Up to Approximately 16 Years)
- Phase 3: Symptomatic AEs as Assessed by the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to Approximately 16 Years)