A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Immunotherapy With or Without Carboplatin in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 155
- 试验地点
- 44
- 主要终点
- Number of participants with DLTs; TEAEs and other safety parameters during the study.
研究概览
简要总结
This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy with or without carboplatin in participants with advanced or metastatic non-small cell lung cancer (NSCLC).
详细描述
The primary objective is to assess the safety and tolerability of Dato-DXd in combination with immunotherapy with or without 4 cycles of carboplatin in participants with advanced or metastatic NSCLC.
Two dose levels of Dato-DXd will be studied in combination with immunotherapy (durvalumab, AZD2936, MEDI5752, or AZD7789) with or without 4 cycles of carboplatin in 15 study cohorts
Each cohort will start with Part 1 (dose escalation or confirmation), where 3 to 9 participants will be assessed for dose-limiting toxicities (DLT) in the first cycle of treatment. if the DLT incidence rate meets the criteria based on the modified toxicity probability interval-2 (mTPI-2), then Part 2 (dose expansion) may be opened.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 ≥18 years old on the day of signing the ICF (local regulatory requirement to consent should be followed).
- •Histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC, without EGFR or ALK genomic alterations (testing not required for participants with documented squamous histology) and no known genomic alterations in other actionable driver kinases with approved therapies. Participants whose tumors harbor KRAS mutations are eligible for this study.
- •For Cohorts 1 to 4, participants must be treatment-naïve or have received and radiologically progressed after only 1 prior line of systemic chemotherapy, without concomitant immune checkpoint inhibitors for advanced or metastatic NSCLC. For Cohorts 4a, 5 to 11, and 14, participants must be treatment-naïve for advanced or metastatic NSCLC. For Cohorts 12 to 13, participants must be CPI acquired resistant after 1 or 2 prior lines of systemic therapy for advanced or metastatic NSCLC, of which 1 should have contained an approved anti-PD-1/PD L
- •Cohort 4a will enroll participants whose tumors have squamous histology only; Cohorts 5 Part 2A and Part 2B as well as Cohorts 12 and 13 will enroll participants whose tumors have non-squamous histology only.
- •Willing and able to undergo a mandatory tumor biopsy. A tumor biopsy that was recently collected (within 3 months of screening) after completion of the most recent anticancer treatment regimen may be substituted for the biopsy collected during screening. For Cohorts 12 and 13, a tumor sample taken ≤24 months prior to screening is acceptable.
- •Has measurable disease per RECIST1.1 within 28 days prior to Cycle 1 Day 1
- •Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 at screening
- •Has adequate bone marrow reserve and organ function at baseline within 7 days prior to Cycle 1 day 1
- •For Cohorts 5 to 14 only: Documented IHC PD-L1 expression per analytically validated Ventana PD-L1 (SP263) IHC assay, 22C3 PharmDx assay, or 28-8 PharmDx assay
排除标准
- •Active or prior documented autoimmune or inflammatory disorders
- •Uncontrolled or significant cardiac disease
- •History of another primary malignancy with exceptions
- •active or uncontrolled hepatitis B or C virus or uncontrolled HIV infection
- •spinal cord compression or clinically active CNS metastases
- •History of (non-infectious) ILD/pneumonitis that required steroids
- •Clinically severe pulmonary compromise resulting from intercurrent pulmonary illness
- •Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- •Clinically significant corneal disease
研究组 & 干预措施
Cohort 8
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: AZD2936 (Drug)
Cohort 10
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: MEDI5752 (Drug)
Cohort 11
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC
干预措施: MEDI5752 (Drug)
Cohort 12
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
干预措施: AZD7789 (Drug)
Cohort 13
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
干预措施: AZD7789 (Drug)
Cohort 14
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC
干预措施: AZD7789 (Drug)
Cohort 3
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Datopotamab deruxtecan (Drug)
Cohort 3
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Carboplatin (Drug)
Cohort 4
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Datopotamab deruxtecan (Drug)
Cohort 4
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Carboplatin (Drug)
Cohort 6
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 5
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 7
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 7
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Carboplatin (Drug)
Cohort 8
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 8
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Carboplatin (Drug)
Cohort 9
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 10
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Carboplatin (Drug)
Cohort 9
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Carboplatin (Drug)
Cohort 10
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 11
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 12
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 13
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with CPI acquired resistant NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 7
Datopotamab deruxtecan (Dato-DXd) + AZD2936 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: AZD2936 (Drug)
Cohort 6
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
干预措施: AZD2936 (Drug)
Cohort 2
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Datopotamab deruxtecan (Drug)
Cohort 1
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Datopotamab deruxtecan (Drug)
Cohort 1
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Durvalumab (Drug)
Cohort 4A
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 14
Datopotamab deruxtecan (Dato-DXd) + AZD7789 in participants with treatment-naïve NSCLC
干预措施: Datopotamab deruxtecan (Drug)
Cohort 4A
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC
干预措施: Durvalumab (Drug)
Cohort 4A
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + carboplatin in participants with treatment-naïve NSCLC
干预措施: Carboplatin (Drug)
Cohort 5
Datopotamab deruxtecan (Dato-DXd) + AZD2936 in participants with treatment-naïve NSCLC
干预措施: AZD2936 (Drug)
Cohort 9
Datopotamab deruxtecan (Dato-DXd) + MEDI5752 + Carboplatin in participants with treatment-naïve NSCLC
干预措施: MEDI5752 (Drug)
Cohort 2
Datopotamab deruxtecan (Dato-DXd) + Durvalumab in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Durvalumab (Drug)
Cohort 4
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Durvalumab (Drug)
Cohort 3
Datopotamab deruxtecan (Dato-DXd) + Durvalumab + Carboplatin in NSCLC participants who are either treatment-naïve or have received only 1 prior line of systemic chemotherapy without concomitant ICI therapy
干预措施: Durvalumab (Drug)
结局指标
主要结局
Number of participants with DLTs; TEAEs and other safety parameters during the study.
时间窗: DLTs: within first cycle (21 days); TEAEs and other safety parameters: when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up (approximately 60 months)
DLTs, TEAEs, SAEs, AESIs, ECOG PS, vital sign measurements, standard clinical laboratory parameters (hematology, clinical chemistry, and urinalysis), ECG parameters, ECHO/MUGA scan findings, and ophthalmologic findings
次要结局
- ORR as assessed by investigator per RECIST Version 1.1(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Duration of Response as assessed by investigator per RECIST version 1.1(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Disease Control Rate as assessed by the investigator per RECIST version 1.1(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Progression-free Survival as assessed by the investigator per RECIST v1.1(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Time to Response as assessed by investigator per RECIST Version 1.1(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Best percentage change in the Sum of Diameters of measurable tumors(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Overall Survival(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Pharmacokinetic Parameter Maximum Plasma/Serum Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a. Serum concentrations of durvalumab and MEDI5752, AZD2936, MEDI5752 and AZD7789.(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Pharmacokinetic Parameter Time to Maximum Plasma/Serum Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a.(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Prevalence of Dato-Dxd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)
- Incidence of Dato-DXd, durvalumab, AZD2936, MEDI5752 and AZD7789 ADA(At the time of the final analysis (when all participants have either discontinued the study or the last participant enrolled in the study has completed at least 9 months of follow-up, approximately 60 months).)