A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,170
- 试验地点
- 463
- 主要终点
- Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants
研究概览
简要总结
This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
详细描述
The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS <50% and advanced or metastatic NSCLC without actionable genomic alternations, as well as participants who are TROP2 NMR+ at baseline. TROP2 NMR will be retrospectively assessed.
Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion. The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.
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
- •Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- •Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is >18 years old).
- •Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of 6 slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study.
- •Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study.
- •Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than those listed in the
排除标准
- •are eligible if the adjuvant/ neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease and should not have progressed on or within the 6 months of completion.
- •Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.
- •Key Exclusion Criteria:
- •Has received prior systemic treatment for advanced/metastatic NSCLC.
- •Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC):
- •Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
- •TROP2-targeted therapy
- •Any anti-PD-1, anti-PD-L1, or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
- •Any other ICIs Subjects who received adjuvant or neoadjuvant therapy other than those listed above are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced or metastatic disease.
- •Has received a live vaccine within 30 days prior to the first dose of study treatment.
- •Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. For any subject receiving an approved severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local guidance. The vaccine manufacturer and the date of administration should be recorded on the electronic case report form (Concomitant Medications page), as should any AEs relating to the vaccine (including hypersensitivity or allergies). Note: Any licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a particular country is allowed in the study as long as the vaccine is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such vaccines will be treated just as any other concomitant therapy.
- •Investigational vaccines (ie, those not licensed or authorized for emergency use) are not allowed.
- •Has spinal cord compression or clinically active untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study drug. Note: A contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI with contrast preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator must delay of study treatment to document stability of CNS metastases with repeat imaging at least 2 weeks later (in which case, repeat of all screening activity may be required).
- •Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including:
- •Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex (based on the 12-lead electrocardiogram [ECG] performed at screening).
- •Myocardial infarction within 6 months prior to Cycle 1 Day
- •History of a serious cardiac arrhythmia requiring treatment
- •Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day
- •Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
- •New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
- •Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).
- •Clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.
研究组 & 干预措施
Dato-DXd + Pembrolizumab
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab.
干预措施: Datopotamab Deruxtecan (Drug)
Dato-DXd + Pembrolizumab + Platinum Chemotherapy
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Datopotamab Deruxtecan (Drug)
Dato-DXd + Pembrolizumab + Platinum Chemotherapy
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Pembrolizumab (Drug)
Dato-DXd + Pembrolizumab + Platinum Chemotherapy
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Carboplatin (Drug)
Dato-DXd + Pembrolizumab + Platinum Chemotherapy
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Cisplatin (Drug)
Dato-DXd + Pembrolizumab
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 200 mg pembrolizumab.
干预措施: Pembrolizumab (Drug)
Pembrolizumab + Pemetrexed + Platinum Chemotherapy
Participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m^2 pemetrexed plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Pembrolizumab (Drug)
Pembrolizumab + Pemetrexed + Platinum Chemotherapy
Participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m^2 pemetrexed plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Pemetrexed (Drug)
Pembrolizumab + Pemetrexed + Platinum Chemotherapy
Participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m^2 pemetrexed plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Carboplatin (Drug)
Pembrolizumab + Pemetrexed + Platinum Chemotherapy
Participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m^2 pemetrexed plus platinum chemotherapy (cisplatin 75 mg/m^2 or carboplatin area under the curve [AUC) 5]).
干预措施: Cisplatin (Drug)
结局指标
主要结局
Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants
时间窗: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive
时间窗: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
Overall Survival in All Randomized Participants
时间窗: From randomization until disease progression or death (whichever occurs first), up to approximately 76 months
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
Overall Survival in All Randomized Participants who are TROP2 NMR positive
时间窗: From randomization until disease progression or death (whichever occurs first), up to approximately 76 months
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
次要结局
- Objective Response Rate by Blinded Independent Central Review in All Randomized Participants(From randomization until disease progression or death (whichever occurs first), up to approximately 43 months)
- Objective Response Rate by Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive(From randomization until disease progression or death (whichever occurs first), up to approximately 43 months)
- Progression-free Survival by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive(From randomization until disease progression or death (whichever occurs first), up to approximately 43 months)
- Objective Response Rate by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive(From randomization until disease progression or death (whichever occurs first), up to approximately 43 months)
- Duration of Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive(From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 43 months)
- Time to Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive(From randomization to date of first objective response (CR or PR), up to approximately 43 months)
- Disease Control Rate by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive(From randomization until disease progression or death (whichever occurs first), up to approximately 43 months)
- Progression-free Survival 2 in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive(From randomization until disease progression or death (whichever occurs first), up to approximately 76 months)
- Time to Deterioration(From randomization until disease progression or death (whichever occurs first), up to approximately 76 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAE)(Up to 76 months)
- Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA(Baseline and up to 76 months)