A Phase 3, Multicenter, Open-Label, Randomized Study to Evaluate Inobrodib in Combination With Pomalidomide and Dexamethasone Versus Standard Available Therapy in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 450
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS) assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The main purpose of this study is to find out whether inobrodib, when given with pomalidomide and dexamethasone, works better than standard treatment for people whose multiple myeloma has come back or has not improved after previous treatment. The study will look at how long people taking part in the study ("Participants") live without their myeloma getting worse, and how many people's myeloma improves (responds) following treatment.
The study will also look at how long participants live overall, how quickly treatment works, how long the response lasts, whether very small amounts of myeloma can still be found after a good response, quality of life, side effects, and the amount of inobrodib in the blood.
Participants receive treatment in 28-day cycles. One group receives inobrodib by mouth twice a day for 4 days, followed by 3 days without inobrodib each week; pomalidomide by mouth once a day on Days 1 to 21 of each cycle; and dexamethasone once each week.
The other group receives 1 standard treatment chosen by the study doctor from the following treatment options: daratumumab, pomalidomide, and dexamethasone; elotuzumab, pomalidomide, and dexamethasone; or carfilzomib and dexamethasone. Some standard treatments are given by injection or infusion at the study site. Other medicines, such as tablets or capsules, may be taken by mouth as instructed by the study team.
Study checks include questions about symptoms and side effects, review of other medicines, physical checks, blood pressure and other vital sign checks, heart tracing tests, blood and urine tests, scans where needed, bone marrow samples, and questionnaires about symptoms and daily life. Participants in the inobrodib group will have extra blood samples to measure the amount of inobrodib in the blood. Some participants may also have extra research blood samples at selected visits.
详细描述
This is a Phase 3, multicenter, open-label, randomized study to evaluate inobrodib in combination with pomalidomide and dexamethasone (InoPd) versus standard available therapy (SAT), defined as Investigator's choice of daratumumab or elotuzumab in combination with pomalidomide and dexamethasone (DPd and EPd, respectively) or carfilzomib in combination with dexamethasone (Kd), in participants with relapsed or refractory multiple myeloma (RRMM).
Participants must be 18 years or older and have received 1 to 4 prior lines of therapy only.
Approximately 450 participants will be randomized 1:1 to be treated with either InoPd (Arm A) or Investigator's choice of SAT (Arm B), which includes DPd, EPd and Kd.
Study treatment should be continued until disease progression, initiation of new anticancer therapy, unacceptable toxicity or the participant meets any criteria for withdrawal from the study.
The dual primary objectives are to compare the efficacy of InoPd with Investigator's choice of SAT in terms of progression-free survival (PFS) and objective response rate (ORR) by Blinded Independent Central Review (BICR) in participants receiving InoPd versus participants receiving SAT.
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
- •Adults aged 18 years or older (or the minimum age of consent under local rules, if that is 18 or over)
- •A diagnosis of multiple myeloma that has either come back (relapsed) or did not respond (refractory) after the most recent treatment
- •Myeloma that can be measured using standard study tests (blood and/or urine tests)
- •Between 1 and 4 previous courses (lines) of myeloma treatment, which must have included both a treatment that targets CD38 (such as daratumumab or isatuximab) and lenalidomide
- •Well enough to carry out daily activities with little or no help (Eastern Cooperative Oncology Group [ECOG] performance status of 0 to 2)
- •Suitable blood test results and adequate kidney and liver function
- •Willingness to use highly effective contraceptive measures (if sexually active) with all sexual partners
排除标准
- •Recent anticancer treatment before starting study treatment: any experimental medicine, chemotherapy, immunotherapy or other anticancer treatment within 14 days or 5 half-lives (whichever is shorter), or certain antibody-based treatments within longer set periods
- •Previous treatment with a medicine that works in the same way as inobrodib (a p300/CBP bromodomain inhibitor)
- •Myeloma that has already stopped responding to pomalidomide (pomalidomide-refractory), unless only short-term pomalidomide was used and the study doctor confirms the person still meets the study rules
- •Unable to receive at least one of the standard treatment options offered in the study, or unable/unwilling to follow the requirements for at least one of those options
- •Taking medicines, herbal supplements or foods (for example, strong CYP3A4 inducers or inhibitors) that would interfere with the study treatment
- •Major surgery within 4 weeks before the first dose of study treatment
- •A live vaccine within 4 weeks before study treatment
- •A recent stem cell transplant, or ongoing transplant-related problems such as graft-versus-host disease
- •Myeloma affecting the brain, spinal fluid or spinal cord, or ongoing pressure on the spinal cord
- •Another active cancer (progressing or needing a change in treatment) in the last 24 months, other than multiple myeloma, apart from certain low-risk or fully treated cancers
- •Serious or uncontrolled medical problems, such as uncontrolled heart, lung, liver, bleeding or diabetes conditions, uncontrolled high blood pressure, or a heart-rhythm problem (including QT prolongation)
- •An active or uncontrolled infection, including certain cases of HIV, hepatitis B or hepatitis C
- •Digestive problems that could stop the study medicines being swallowed or properly absorbed
- •Pregnant or breastfeeding, or planning to become pregnant, father a child or donate sperm during treatment or the required post-treatment period
- •Any illness or medical history that could affect safety, the ability to follow study requirements, or the interpretation of study results
结局指标
主要结局
Progression-free Survival (PFS) assessed by Blinded Independent Central Review (BICR)
时间窗: From randomization until progressive disease or death, assessed every 28 days and followed until the final PFS analysis after approximately 330 PFS events; estimated up to approximately 38 months after the start of enrollment
Defined as the time from randomization until the earliest date of PD based on International Myeloma Working Group (IMWG) criteria assessed by BICR, or death due to any cause
Objective Response Rate (ORR) assessed by BICR
时间窗: From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or the ORR data cutoff, whichever occurs first; disease response assessed every 28 days (up to 48 months)
Defined as the percentage of participants with a confirmed PR or better, based on IMWG criteria assessed by BICR
次要结局
- Overall Survival (OS)(From randomization until death from any cause or the final OS analysis after approximately 329 deaths; survival status assessed every 12 weeks after disease progression or treatment discontinuation (up to 48 months))
- PFS Assessed by the Investigator(From randomization until progressive disease or death; disease assessments performed every 28 days until confirmed progression, death, withdrawal, loss to follow-up, or end of study (up to 48 months))
- ORR Assessed by the Investigator(From randomization until confirmed progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months))
- Minimal Residual Disease (MRD) Negativity Rate(At confirmed CR or better; if MRD negativity is not demonstrated at CR, reassessed within 3 to 6 months after confirmation of CR or better (up to 48 months))
- Duration of Response (DoR) Assessed by BICR(From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months))
- DoR Assessed by the Investigator(From the first documented confirmed response until progressive disease or death; assessed every 28 days until progression or end of study (up to 48 months))
- Time to Response (TTR) Assessed by BICR(From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months))
- TTR Assessed by the Investigator(From randomization to the first documented confirmed response; assessed every 28 days (up to 48 months))
- Very Good Partial Response (VGPR) or Better Rate Assessed by BICR(From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months))
- VGPR or Better Rate Assessed by the Investigator(From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months))
- Complete Response (CR) or Better Rate Assessed by BICR(From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months))
- CR or Better Rate Assessed by the Investigator(From randomization until progressive disease, initiation of subsequent anticancer therapy, death, withdrawal, or end of study; assessed every 28 days (up to 48 months))
- Change From Baseline in EORTC QLQ-C30 Scores(Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months))
- Change From Baseline in EORTC QLQ-MY20 Disease Symptoms Score(Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months))
- Change From Baseline in EQ-5D-5L Health Status(Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months))
- Treatment Side-Effect Bother Assessed by FACT-GP5(Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months))
- Symptomatic Adverse Events Assessed by PRO-CTCAE(Assessed at baseline and protocol-specified visits during the first year, then every 3 months until treatment discontinuation, withdrawal, or the end of study (up to 48 months))
- Participants With Treatment-Emergent Adverse Events(Assessed from the first dose of study treatment through 28 days after the last dose (up to 48 months))
- Change From Baseline in Electrocardiogram Parameters(Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months))
- Change From Baseline in Vital Signs(Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months))
- Participants With Laboratory Abnormalities(Assessed at baseline and protocol-specified visits during treatment through the 28-day post-treatment follow-up visit (up to 48 months))
- Plasma Concentrations of Inobrodib(Assessed at protocol-specified predose and postdose time points during treatment (up to 48 months))