NCT04744831已完成2 期
A Phase 2, Multicenter, Randomized, Study of Trastuzumab Deruxtecan in Participants With HER2-overexpressing Locally Advanced, Unresectable or Metastatic Colorectal Cancer (DESTINY-CRC02)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 122
- 试验地点
- 63
- 主要终点
- Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer
研究概览
简要总结
This study will evaluate the efficacy, safety, and pharmacokinetics of Trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor 2 (HER2)-overexpressing locally advanced, unresectable, or metastatic colorectal cancer (mCRC).
详细描述
This 2-stage study will evaluate participants with locally advanced, unresectable, or metastatic HER2-overexpressing colorectal cancer (CRC) (immunohistochemistry [IHC] 3+ or IHC 2+/ in situ hybridization [ISH]+) of v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type and either rat sarcoma viral oncogenes homologue (RAS) wild-type or mutant tumor type, previously treated with standard therapy. In the first stage, participants will be randomized 1:1 with 2 doses of T-DXd. After Stage 1 enrollment is complete, all further eligible participants will be registered to T-DXd administered IV in Stage 2. Participants will receive the assigned dose of T-DXd until progression of disease or the participant meets one of the discontinuation criteria.
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
- Double (Participant, Investigator)
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
- •Participants must meet all of the following criteria to be eligible for randomization/registration into the study:
- •Adults aged ≥20 years in Japan, Taiwan, and Korea, or those aged ≥18 years in other countries, at the time the Informed Consent Forms (ICFs) are signed.
- •Pathologically-documented, unresectable, recurrent, or metastatic colorectal adenocarcinoma. Participants must have v-raf murine sarcoma viral oncogene homologue B1 (BRAF) wild-type cancer and rat sarcoma viral oncogenes homologue (RAS) status identified in primary or metastatic site.
- •The following therapies should be included in prior lines of therapy:
- •Fluoropyrimidine, oxaliplatin, and irinotecan, unless contraindicated
- •Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type and if clinically indicated
- •Anti-vascular endothelial growth factor (VEGF) treatment, if clinically indicated
- •Anti-programmed death ligand 1 (PD-(L)-1) therapy, if the tumor is microsatellite instability (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high, if clinically indicated
- •Confirmed human epidermal growth factor 2 (HER2)-overexpressing status assessed by central laboratory and defined as immunohistochemistry (IHC) 3+ or IHC 2+/ in situ hybridization (ISH) +.
- •Presence of at least one measurable lesion assessed by the Investigator per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or
- •Has left ventricular ejection fraction (LVEF) ≥50% within 28 days before randomization/registration.
排除标准
- •Participants who meet any of the following criteria will be disqualified from entering the study:
- •Medical history of myocardial infarction (MI) within 6 months before randomization/registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above the upper limit of normal (ULN) at Screening (as defined by the manufacturer), and without any MI-related symptoms, should have a cardiologic consultation before randomization/registration to rule out MI.
- •Has a corrected QT interval corrected with Fridericia's formula (QTcF) prolongation to >470 msec (female participants) or >450 msec (male participants) based on the average of the Screening triplicate 12-lead electrocardiograms (ECGs).
- •Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- •Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the randomization/registration, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.).
- •Any autoimmune, connective tissue, or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented, or a suspicion of, pulmonary involvement at the time of Screening.
- •Prior pneumonectomy.
- •Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole-brain radiotherapy and randomization/registration.
- •Participants with leptomeningeal carcinomatosis.
- •Has known human immunodeficiency virus (HIV) infection.
- •Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days before study randomization/registration. Participants with past or resolved hepatitis B virus (HBV) infection are eligible if hepatitis B surface antigen (HBsAg) negative (-) and antibody to hepatitis B core antigen (anti-HBc) positive (+).
- •Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
- •Previous treatment with a DXd-containing antibody-drug conjugate (ADC).
研究组 & 干预措施
T-DXd 5.4 mg/kg Q3W
Experimental
Participants will be randomized to receive intravenous T-DXd administered at a dose of 5.4 mg/kg every 3 weeks (Q3W).
干预措施: DS-8201a 5.4 mg/kg Q3W (Drug)
T-DXd 6.4 mg/kg Q3W
Experimental
Participants will be randomized to receive intravenous T-DXd administered at a dose of 6.4 mg/kg every 3 weeks (Q3W).
干预措施: DS-8201a 6.4 mg/kg Q3W (Drug)
结局指标
主要结局
Percentage of Participants With Objective Response Rate (ORR) Based on Blinded Independent Central Review Following IV Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2-overexpressing Metastatic Colorectal Cancer
时间窗: 6 months post-dose administration to data cut off, up to 20 months
Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.
次要结局
- Confirmed Objective Response Rate by Investigator Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer(From first dose administration to data cut off, up to approximately 19 months)
- Duration of Response Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer(From the first documented evidence of a response (complete or partial) until disease progression or death, up to approximately 19 months.)
- Disease Control Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer(From first dose administration to data cut off, up to approximately 19 months.)
- Clinical Benefit Rate Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) -Overexpressing Metastatic Colorectal Cancer(From first dose administration to data cut off, up to approximately 19 months.)
- Progression Free Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer(From randomization to data cut off, up to approximately 19 months.)
- Overall Survival Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer(From randomization to data cut off, up to approximately 19 months.)
- Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of T-DXd in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Overexpressing Metastatic Colorectal Cancer(From first dose administration to data cut off, up to approximately 19 months.)
- Serum Concentration of T-DXd(C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI))
- Serum Concentration of Total Anti-Human Epidermal Growth Factor Receptor 2 (HER2) Antibody(C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI))
- Serum Concentration of Active Metabolite MAAA-1181a(C1D1 (Before infusion (BI), end of infusion (EOI) and 5 hours after infusion), C1D8 (7 days after infusion), C1D15 (14 days after infusion), C2D1 (BI and EOI), C3D1 (BI and EOI), C4D1, (BI and EOI), C6D1 (BI and EOI))
- Percentage of Participants Positive for Treatment-emergent Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (NAb) in Participants Who Were Administered T-DXd(From baseline to data cut off, up to approximately 19 months)
研究者
研究点 (63)
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