NCT06497556进行中（未招募）3 期
A Phase III, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Patients With Previously Treated KRAS G12C-Positive 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
- 进行中（未招募）
- 入组人数
- 338
- 试验地点
- 344
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).
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
- •Unequivocal histologically or cytologically confirmed diagnosis of metastatic or locally advanced NSCLC not amenable to treatment with surgical resection or combined chemoradiation
- •Disease progression during or after treatment with at least one prior systemic therapy but no more than three lines of prior systemic therapy in the advanced or metastatic setting
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Documentation of the presence of a KRAS G12C mutation
- •Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 (15 preferred) unstained, freshly cut, serial slides with an associated pathology report
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy of >= 12 weeks
排除标准
- •Known hypersensitivity to any of the components of divarasib, or sotorasib or adagrasib
- •Malabsorption syndrome or other condition that would interfere with enteral absorption
- •Known concomitant second oncogenic driver
- •Mixed small-cell lung cancer or large cell neuroendocrine histology
- •Known and untreated, or active central nervous system (CNS) metastases
- •Leptomeningeal disease or carcinomatous meningitis
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently
- •Any infection that, in the opinion of the investigator, could impact patient safety, or treatment with therapeutic oral or IV antibiotics within 14 days prior to Day 1 of Cycle 1
- •Prior treatment with any KRAS G12C inhibitor or pan-KRAS/RAS inhibitor
- •More than 30 Gy of radiotherapy to the lung within 6 months of randomization
- •Uncontrolled tumor-related pain
- •Unresolved toxicities from prior anticancer therapy
- •History of malignancy within 5 years prior to screening, with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
研究组 & 干预措施
KRAS G12C inhibitor
Active Comparator
Participants will receive sotorasib orally QD or adagrasib orally twice a day (BID)
干预措施: Sotorasib (Drug)
KRAS G12C inhibitor
Active Comparator
Participants will receive sotorasib orally QD or adagrasib orally twice a day (BID)
干预措施: Adagrasib (Drug)
Divarasib
Experimental
Participants will receive divarasib orally, once daily (QD).
干预措施: Divarasib (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 4 years
PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) according to RECIST v1.1, or death from any cause (whichever occurs first)
次要结局
- Overall Survival (OS)(Up to approximately 4 years)
- Time to Confirmed Deterioration (TTCD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Dyspnea Item and Physical Functioning Scale(Baseline up to approximately 4 years)
- TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale(Baseline up to approximately 4 years)
- Duration of Response (DOR)(Up to approximately 4 years)
- Percentage of Participants with Adverse Events (AEs)(Up to approximately 4 years)
- Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to approximately 4 years)
- Change from Baseline in Diarrhea, Nausea, Vomiting, Anorexia, Alopecia, Dyspnea, Cough, Constipation, Myalgia, Headache, and Rash/Acne as Assessed Through use of the NCI PRO-CTCAE(Baseline up to approximately 4 years)
- Frequency of Participants' Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the single-item EORTC Item List (IL46)(Up to approximately 4 years)
- Change from Baseline in Cough, Chest Pain, Dyspnea, Physical and Role Functioning, and Global Health Status score/Quality of Life Score (GHS/QoL) at Each Timepoint as Assessed Through use of the EORTC QLQ-LC13 and QLQ-C30(Baseline up to approximately 4 years)
- TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales(Up to approximately 4 years)
- TTCD on the Chest Pain Scale of the QLQ-LC13 Scales(Up to approximately 4 years)
- Overall Survival (OS)(Up to approximately 4 years)
- Confirmed Objective Response(Up to approximately 4 years)
- Time to Confirmed Deterioration (TTCD) on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Dyspnea Item and Physical Functioning Scale(Baseline up to approximately 4 years)
- TTCD on the EORTC Quality-of-Life Questionnaire-Supplemental Lung Cancer Module (QLQ-LC13) Cough Scale(Baseline up to approximately 4 years)
- Duration of Response (DOR)(Up to approximately 4 years)
- Percentage of Participants with Adverse Events (AEs)(Up to approximately 4 years)
- Number of Participants Reporting Presence, Frequency, Severity, and/or Degree of Interference with Daily Function of Symptomatic Treatment Toxicities Assessed by NCI Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to approximately 4 years)
- Change from Baseline in Diarrhea, Nausea, Vomiting, Anorexia, Alopecia, Dyspnea, Cough, Constipation, Myalgia, Headache, and Rash/Acne as Assessed Through use of the NCI PRO-CTCAE(Baseline up to approximately 4 years)
- Frequency of Participants' Response of the Degree they are Troubled with Treatment Symptoms, as Assessed Through use of the single-item EORTC Item List (IL46)(Up to approximately 4 years)
- Change from Baseline in Cough, Chest Pain, Dyspnea, Physical and Role Functioning, and Global Health Status score/Quality of Life Score (GHS/QoL) at Each Timepoint as Assessed Through use of the EORTC QLQ-LC13 and QLQ-C30(Baseline up to approximately 4 years)
- TTCD on the EORTC QLQ-C30 Role Functioning and GHS/QoL scales(Up to approximately 4 years)
- TTCD on the Chest Pain Scale of the QLQ-LC13 Scales(Up to approximately 4 years)
研究者
研究点 (344)
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