Phase 1/2, Multicentre, Open-label, Multiple-cohort Study of Dato-DXd in Chinese Patients With Advanced Non-small-cell Lung Cancer, Triple-negative Breast Cancer, Gastric/Gastroesophageal Junction Cancer, Urothelial Cancer, and Other Solid Tumours (TROPION-PanTumor02)
概览
- 阶段
- 1 期
- 干预措施
- Datopotamab Deruxtecan (Dato-DXd)
- 疾病 / 适应症
- Carcinoma, Non-Small-Cell Lung
- 发起方
- AstraZeneca
- 入组人数
- 119
- 试验地点
- 21
- 主要终点
- Confirmed Objective Response Rate(ORR) Assessed by Independent Central Review(ICR)
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
Researchers are looking for a better way to treat advanced Triple-Negative Breast Cancer (TNBC) and Non-Small-Cell Lung Cancer (NSCLC). "Advanced" usually means that the cancer keeps growing even with treatment. The cancer may also be "metastatic", which means that it has spread to other parts of the body or the surrounding tissue.
The study drug, Datopotamab deruxtecan, is designed to work by attaching to the tumor cells and stopping the tumor growth. Datopotamab deruxtecan is also known as Dato-DXd.
In this study, the researchers want to find out how well Dato-DXd works to stop tumors from growing in Chinese participants with NCSLC or TNBC. This is the first time Dato-DXd is being studied in Chinese population.
Participants in this study will get Dato-DXd through a needle as an injection. They will get 1 dose of Dato-DXd every 3 weeks until their cancer gets worse or they leave the study for another reason.
Participants will visit their study sites at least once every 3 weeks for as long as they are in the study. The study doctors will take blood samples every 3 weeks and take images of the participants' tumors every 6 weeks until the participant leaves the study.
详细描述
This is a Phase 1/Phase 2, multicentre, open-label, multiple-cohort study, which is designed to evaluate the efficacy, safety, Pharmacokinetic, and immunogenicity of Dato-DXd in adult Chinese participants with advanced or metastatic solid tumours. It is a single-arm study with no blinding. This study is divided into different cohorts. Participants of the same cohort are with the same tumour type. The starting cohorts are Cohort 1 (NSCLC) and Cohort 2 (TNBC). Future cohorts will consist of other advanced or metastatic solid tumour types, including, but not limited to, advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma or urothelial carcinoma that is refractory or intolerant to SoC therapy or for which no Standard of Care therapy is available. Cohort 1 and Cohort 2 will be prioritised for immediate enrolment and the protocol will be amended as needed for the future cohorts. Cohort 1: The target population of Cohort 1 is adult Chinese participants with advanced or metastatic NSCLC with or without actionable genomic alterations(AGAs) (ie, alterations in genes with approved therapies, such as EGFR, ALK, or other known AGAs). Eligible participants without AGAs will have been previously treated with platinum-based chemotherapy and anti-PD-1/anti-PD-L1 monoclonal antibody either in combination or sequentially. Participants without AGAs who received anti-PD-1/anti-PD-L1 monoclonal antibody as frontline therapy may have received the combination of platinum-based chemotherapy and anti-PD-1/anti-PD-L1 monoclonal antibody in the second-line setting. Eligible participants with AGAs will have been previously treated with one or two prior lines of applicable targeted therapy that is approved for the participant's genomic alteration and platinum-based chemotherapy as the only prior line of cytotoxic therapy. Participants with AGAs may have received up to one anti-PD-1/anti-PD-L1 monoclonal antibody treatment alone or in combination with chemotherapy. A total of approximately 40 eligible participants in China will be enrolled in this cohort, including approximately 6 participants with AGAs. Cohort 2: The target population of Cohort 2 is adult Chinese participants with inoperable locally advanced or metastatic TNBC who have received at least 2 prior chemotherapy regimens for advanced breast cancer, counting the (neo)adjuvant therapy as a prior chemotherapy regimen if progression occurred within 12 months after completion of the therapy (DFI ≤ 12 months). A total of approximately 78 eligible participants in China will be enrolled in this cohort. Cohort 2 will enroll at most around 20% (approximately N=15) of enrolled participants with a DFI ≤ 12 months. Enrolled participants will be treated with Dato-DXd at 6.0 mg/kg via an IV infusion on Day 1,every 3 weeks. The primary objective of the study is to estimate the effectiveness of Dato-DXd by assessment of confirmed ORR by independent central review.
研究者
入排标准
入选标准
- •Capable of giving signed informed consent.
- •Participant must be ≥ 18 years at the time of screening.
- •Eastern Cooperative Oncology Group performance status of 0 or
- •At least one lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline and is suitable for accurate repeated measurements.
- •Additional Inclusion Criteria for Cohort 1 (NSCLC):
- •\- Histologically or cytologically documented Stage IIIB or IIIC NSCLC disease not amenable for surgical resection or definitive chemoradiation or Stage IV NSCLC disease at the beginning of study intervention.
- •For the subset of participants without AGAs:
- •Documented negative test results for EGFR and ALK genomic alterations. If test results for EGFR and ALK are not available, participants are required to undergo testing performed locally for these genomic alterations.
- •Participants must meet one of the required prior therapy requirements for advanced or metastatic NSCLC.
- •For the subset of participants with AGAs:
排除标准
- •Has leptomeningeal carcinomatosis or metastasis
- •Has clinically significant corneal disease
- •Has known active hepatitis or uncontrolled hepatitis B or C infection
- •Has a history of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Prior exposure to specific therapies without an adequate treatment washout period prior to enrolment.
- •Additional Exclusion Criteria for Cohort 1 (NSCLC):
- •\- Has mixed SCLC and NSCLC histology.
研究组 & 干预措施
Dato-DXd Arm
This single-arm study consists of multiple cohorts, divided by indication.
干预措施: Datopotamab Deruxtecan (Dato-DXd)
结局指标
主要结局
Confirmed Objective Response Rate(ORR) Assessed by Independent Central Review(ICR)
时间窗: TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.
Confirmed ORR is defined as the proportion of participants in each cohort who have a confirmed CR or confirmed PR, as assessed by ICR per RECIST 1.1.
次要结局
- Confirmed Objective Response Rate(ORR) Assessed by Investigator(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Duration of Response (DoR), Assessed by Investigator(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Disease Control Rate (DCR), Assessed by ICR(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Best Overall Response (BoR) , Assessed by ICR(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Time To Response (TTR) , Assessed by ICR(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Progression-Free Survival (PFS) , Assessed by ICR(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Overall Survival (OS)(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Progression-Free Survival (PFS) , Assessed by Investigator(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Disease Control Rate (DCR), Assessed by Investigator(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Best Overall Response (BoR) , Assessed by Investigator(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Time To Response (TTR) , Assessed by Investigator(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Area Under the Plasma Concentration- Time Curve (AUC) _ Total Anti-TROP2 Antibody(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) _ Total Anti-TROP2 Antibody(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Area Under the Plasma Concentration- Time Curve (AUC) _Dato-DXd(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) _ Dato-DXd(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Area Under the Plasma Concentration- Time Curve (AUC) _ MAAA-1181a(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) _ MAAA-1181a(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Time to Maximum Plasma Concentration (Tmax) _Total Anti-TROP2 Antibody(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Time to Maximum Plasma Concentration (Tmax) _Dato-DXd(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Pharmacokinetic Parameter: Time to Maximum Plasma Concentration (Tmax) _ MAAA-1181a(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Immunogenicity of Dato-DXd(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)
- Duration of Response (DoR), Assessed by ICR(TNBC cohort: from enrollment to 13 months post last subject dose with a median of 12 months follow up. NSCLC cohort: from enrollment to 20 months post last subject dose with a median of 16.7 months follow up.)