A Phase III, Multicentre, Randomised, Open-label Study to Compare the Efficacy and Safety of AZD0486 Plus Rituximab Versus Chemotherapy Plus Rituximab in Previously Untreated Participants With Follicular Lymphoma (SOUNDTRACK-F1)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 1,018
- 试验地点
- 235
- 主要终点
- SRI Primary: Incidence, nature and severity of AEs and SAEs. Incidence and nature of study drug discontinuations, dose reductions, and dose delays due to AEs
研究概览
简要总结
This is a global, randomised, Phase III, multicentre, open-label study evaluating the efficacy, safety and the degree of added benefit of the Surovatamig (AZD0486) plus rituximab combination compared to Investigator's choice of 3 standard immunochemotherapy regimen, conducted in participants with untreated FL.
详细描述
The study consists of 2 sequential parts.
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Safety Run-in - this part will compare dose levels of Surovatamig (AZD0486) in combination with rituximab in order to establish the RP3D.
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Phase III - The Phase III part will assess the superiority of Surovatamig (AZD0486) at RP3D in combination with rituximab, compared to Investigator's choice between 3 standard chemoimmunotherapy regimens. Phase 3 consists of 3 arms
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Arm A: treatment with Surovatamig plus rituximab Schedule A
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Arm B: treatment with Surovatamig plus rituximab Schedule B
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Arm C (Comparator arm): one of the following standard regimens per Investigator's choice: R-CVP + rituximab maintenance, R-CHOP + rituximab maintenance or B-R + rituximab maintenance
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be at least 18 years of age, inclusive, at the time of signing the ICF.
- •Histologically confirmed diagnosis of classic FL per WHO 2022 classification
- •ECOG performance status of 0 to 2
- •No prior systemic lymphoma-directed therapy
- •Need for systemic treatment meeting at least 1 GELF criteria
- •FDG-avid and measurable disease
- •Stage II to IV and FLIPI 2-5 [Phase III only]
- •Adequate liver, hematological, renal and cardiac function.
- •The above is a summary, other inclusion criteria details may apply
排除标准
- •Follicular large B-cell lymphoma (WHO 2022 classification), formerly Follicular lymphoma Grade 3B (WHO 2016 classification) or suspicion for histologic transformation to high-grade/aggressive lymphoma
- •Contra-indication to BR, RCVP, and R-CHOP
- •Participants with or history of CNS lymphoma
- •History of a clinically relevant CNS medical condition or pathology that required treatment in the preceding year, is currently symptomatic or that which the treating investigator considers to have the potential to interfere with the evaluation of safety
- •Presence of >5000 circulating lymphoma cells
- •Active or uncontrolled infection (including EBV) requiring systemic therapy and which places participant at unacceptable risk if he/she were to participate in the study. If a participant has a history of COVID-19 within 1 month of C1D1 or contracts COVID while on study treatment, participant must have 2 consecutive negative tests (PCR testing is preferable) performed at least 48 hours apart prior to resuming dosing. All symptoms related to COVID-19 infection should have fully resolved before initiating or resuming treatment
- •Known history of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)
- •The above is a summary, other exclusion criteria details may apply
研究组 & 干预措施
Chemoimmunotherapy
Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP, R-CVP, or B-R followed by rituximab maintenance)
干预措施: BR (Drug)
Chemoimmunotherapy
Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP, R-CVP, or B-R followed by rituximab maintenance)
干预措施: R-CVP (Drug)
Chemoimmunotherapy
Investigator's choice between 3 standard immunochemotherapy regimen (R-CHOP, R-CVP, or B-R followed by rituximab maintenance)
干预措施: R-CHOP (Drug)
Rituximab, Surovatamig - B
Surovatamig regimen B plus rituximab
干预措施: Surovatamig (Drug)
Rituximab, Surovatamig - A
Surovatamig regimen A plus rituximab
干预措施: Surovatamig (Drug)
结局指标
主要结局
SRI Primary: Incidence, nature and severity of AEs and SAEs. Incidence and nature of study drug discontinuations, dose reductions, and dose delays due to AEs
时间窗: Up to 10 years
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures.
SRI Primary: Determination of the recommended Phase III dose (RP3D)
时间窗: Up to 1 year
The RP3D will be the dose of Surovatamig selected for the Phase 3 part based on safety data compiled during the safety run-in part
Phase 3 Dual Primary: To demonstrate the superiority of Surovatamig plus rituximab compared to Investigator's choice of SoC chemoimmunotherapy
时间窗: Up to 10 years
PFS, based on Lugano 2014 Response Criteria, as assessed by BICR.
SRI Primary: Incidence, nature and severity of AEs and SAEs. Incidence and nature of study drug discontinuations, dose reductions, and dose delays due to AEs
时间窗: Up to 10 years
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in physical examination and safety procedures.
SRI Primary: Determination of the recommended Phase III dose (RP3D)
时间窗: Up to 1 year
The RP3D will be the dose of AZD0486 selected for the Phase 3 part based on safety data compiled during the safety run-in part
Phase 3 Dual Primary: To demonstrate the superiority of AZD0486 plus rituximab compared to Investigator's choice of SoC chemoimmunotherapy
时间窗: Up to 10 years
ORR at EoI, based on Lugano 2014 Response Criteria, as assessed by BICR.
次要结局
- Safety Run In and Phase 3: CR at EoI(Up to 10 years)
- Safety Run in and Phase 3: ORR at EoI (Investigator assessed)(Up to 10 years)
- Safety Run In and Phase 3: CR Rate(Up to 10 years)
- Safety Run In and Phase 3: DoR(up to 10 years)
- Safety Run In and Phase 3: PFS (Investigator assessed)(Up to 10 years)
- Safety Run In and Phase 3: OS(Up to 10 years)
- Phase 3: CR rate at 30 months (CR30)(Up to 30 months)
- Phase 3: Time to First Subsequent Therapy or Death (TFST)(Up to 10 Years)
- Phase 3: Time from randomisation to second progression or death (PFS2)(Up to 10 Years)
- Phase 3: Time to First Subsequent Therapy or Death (TFST)(Up to 10 Years)
- Safety Run In and Phase 3: OS(Up to 10 years)
- Safety Run in and Phase 3: ORR at EoI (Investigator assessed)(Up to 10 years)
- Safety Run In and Phase 3: DoR(up to 10 years)
- Phase 3: Time from randomisation to second progression or death (PFS2)(Up to 10 Years)
- Safety Run In and Phase 3: CR Rate(Up to 10 years)
- Phase 3: CR rate at 30 months (CR30)(Up to 30 months)
- Safety Run In and Phase 3: CR at EoI(Up to 10 years)
- Safety Run In and Phase 3: PFS (Investigator assessed)(Up to 10 years)