NCT06350097招募中3 期
A Phase III, Open-label, Randomised Study of Osimertinib With or Without Datopotamab Deruxtecan (Dato-DXd), as First-line Treatment in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation-positive, Locally Advanced or Metastatic Non-small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 582
- 试验地点
- 167
- 主要终点
- To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants.
研究概览
简要总结
The purpose of this study is to evaluate efficacy and safety of osimertinib (tablet) in combination with Dato-DXd (i.v. infusion) compared with osimertinib (tablet) monotherapyas a first-line therapy in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC.
Study details include:
- The study duration will be event-driven, with an estimated duration of approximately 8 years.
- Participants may receive study treatment until disease progression, unacceptable toxicity, or other specific discontinuation criteria are met.
- The visit frequency will be every 3 weeks during the treatment period.
Note: Participants on osimertinib treatment(osimertinib only arm or who have discontinued Dato-DXd while are still receiving osimertinib) are required to attend visits to perform assessments every 6 weeks from Cycle 7 until Cycle 17 and then visits every 12 weeks until disease progression or IP discontinuation. Participants who are receiving osimertinib + Dato-DXd are still required to attend visit to perform assessment every 3 weeks (q3w) per SoA.
详细描述
This is a global Phase III, open-label, randomised, multicentre study assessing the efficacy and safety of osimertinib in combination with Datopotamab Deruxtecan compared with osimertinib in participants with locally advanced or metastatic EGFRm (Ex19del and/or L858R) NSCLC who have not received any prior therapy for advanced disease.
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
- •Participant must be ≥ 18 years.
- •Type of Participant and Disease Characteristics
- •Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed if adenocarcinoma is the predominant histology. Mixed small-cell lung cancer and NSCLC histology, and sarcomatoid variant of NSCLC is ineligible.
- •Stage IIIB or IIIC or Stage IV metastatic NSCLC or recurrent NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative surgery or definitive chemoradiation at the time of randomisation.
- •Participants must not have received prior EGFR TKIs or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.
- •The tumour harbors at least 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other genomic alterations, which may include EGFR T790M, assessed by a CLIA-certified (US sites) or an accredited (outside of the US) local laboratory or by central prospective tissue testing.
- •For participants enrolled in randomisation period, mandatory provision of an unstained, archival tumour tissue sample in a quantity sufficient to allow for central confirmation of the EGFR mutation status.
- •WHO performance status of 0 or
- •At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have short axis ≥15 mm) with CT or MRI and is suitable for accurate repeated measurements.
- •Adequate bone marrow reserve and organ function before the first dose of study intervention.
排除标准
- •As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, history of allogenic organ transplant which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
- •Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of osimertinib.
- •History of another primary malignancy.
- •Spinal cord compression and/or unstable brain metastases.
- •Clinically significant corneal disease.
- •Has active or uncontrolled hepatitis B or C virus infection, as defined by Protocol.
- •Past medical history of ILD/penumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- •Has clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
研究组 & 干预措施
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan
Experimental
Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.
干预措施: Osimertinib (Drug)
Arm 1: Osimertinib in combination with Datopotamab Deruxtecan
Experimental
Participants in this group will receive osimertinib 80 mg QD as oral tablet with Datopotamab Deruxtecan 6mg/kg as i.v. infusion q3w of Day 1 of every 21-day cycle.
干预措施: Datopotamab Deruxtecan (Drug)
Arm 2: Osimertinib monotherapy
Active Comparator
Participants in this group will receive osimertinib 80 mg QD as oral tablet.
干预措施: Osimertinib (Drug)
结局指标
主要结局
To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Progression Free Survival (PFS) by BICR in all randomised participants.
时间窗: It is anticipated that it will be performed approximately 3 years after the first participant is randomised.
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression).
次要结局
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants.(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Response Rate (ORR) in all randomised participants with measurable disease at baseline.(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Survival (OS) in all randomised participants.(It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on Central nervous system (CNS) metastases in participants with CNS metastases at baseline(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Duration of Response (DoR) in all randomised participants with measurable disease at baseline.(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants(It is anticipated that it will be analyzed by time of PFS primary which is about 3 years after the first participant has been randomised.)
- To assess the Pharmacokinetics (PK) of osimertinib and Datopotamab Deruxtecan(It is anticipated that it will be performed approximately 3 years after the first participant has been randomised.)
- To investigate the immunogenicity of Datopotamab Deruxtecan(It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.)
- To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations(It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.)
- To assess the Pharmacokinetics (PK) of osimertinib and Datopotamab Deruxtecan(It is anticipated that it will be performed approximately 3 years after the first participant has been randomised.)
- To investigate the immunogenicity of Datopotamab Deruxtecan(It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.)
- To compare the local EGFR mutation test result used for patient selection with the retrospective central cobas® EGFR Mutation Test v2 results from baseline tumour samples(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan vs. osimertinib monotherapy based on the cobas® EGFR Mutation Test v2 plasma screening test result for Ex19del or L858R EGFR mutations(It is anticipated that it will be performed approximately 3 years after the first participant has been randomised, together with PFS primary.)
- To demonstrate the superiority of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Survival (OS) in all randomised participants.(It is anticipated that it will be performed approximately 7 years after the first participant has been randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS on Central nervous system (CNS) metastases in participants with CNS metastases at baseline(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS by investigator in all randomised participants.(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Overall Response Rate (ORR) in all randomised participants with measurable disease at baseline.(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of Duration of Response (DoR) in all randomised participants with measurable disease at baseline.(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib on the prevention of CNS metastases(It is anticipated that it will be performed approximately 3 years after the first participant is randomised.)
- To demonstrate the effectiveness of osimertinib in combination with Datopotamab Deruxtecan relative to osimertinib by assessment of PFS2 in all randomised participants(It is anticipated that it will be analyzed by time of PFS primary which is about 3 years after the first participant has been randomised.)
研究者
研究点 (167)
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