2023-507171-22-00招募中2 期
A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination with Other Anti-Cancer Therapies in Patients with Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer with a KRAS G12C Mutation
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 116
- 试验地点
- 20
- 主要终点
- 1. Occurrence of adverse events
研究概览
简要总结
To evaluate the safety and tolerability of divarasib in combination with pembrolizumab (Cohort A) and divarasib in combination with pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B)
研究设计
- 分配方式
- Randomized
- 主要目的
- Overall Design
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Histologically or cytologically documented locally advanced unresectable or metastatic non-squamous NSCLC that is not eligible for curative surgery and/or definitive chemoradiotherapy
- •No prior systemic treatment for advanced unresectable or metastatic NSCLC
- •Adequate cardiovascular function as evidenced by the following: no significant cardiovascular disease within 3 months prior to initiation of study treatment and baseline corrected QT interval <=470 ms
- •Pretreatment tumor tissue along with an associated pathology report is required for all participants enrolled on study. Representative tumor specimens must be in formalin‑fixed, paraffin-embedded (FFPE) blocks (preferred) or 15 unstained, freshly cut, serial slides. Although 15 slides are required, if only 10 slides are available, the participant may be eligible for the study following consultation with the Sponsor.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- •Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
排除标准
- •Known concomitant second oncogenic driver with available targeted treatment
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Prior treatment with a KRAS G12C inhibitor
- •Known hypersensitivity to any of the components of divarasib or pembrolizumab; or known hypersensitivity to pemetrexed, carboplatin, or cisplatin (Cohort B only)
- •History of malignancy other than NSCLC within 5 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate more >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
- •Uncontrolled tumor-related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
- •Significant cardiovascular disease within 3 months prior to initiation of study treatment , including any of the following: hypertensive crisis or encephalopathy; unstable angina; transient ischemic attack or stroke; congestive heart failure (NYHA class 2 or higher); serious cardiac arrythmia requiring treatment; history of thromboembolic events
结局指标
主要结局
1. Occurrence of adverse events
1. Occurrence of adverse events
2. Change from baseline at each visit in targeted safety parameters
2. Change from baseline at each visit in targeted safety parameters
次要结局
- 1. Objective response rate
- 2. Duration of response
- 3. Progression free survival
- 4. Presence, frequency of occurrence, severity, and/or degree of interference with daily function of symptomatic side effects as assessed through use of the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO‑CTCAE)
- 5. Change from baseline in symptomatic side effects, as assessed through use of the PRO-CTCAE
- 6. Proportion of participants reporting "frequent" or "almost constant" diarrhea during the first three cycles of treatment according to the PRO-CTCAE criteria
- 7. Proportion of participants reporting "severe" or "very severe" nausea or vomiting during the first three cycles of treatment according to the PRO-CTCAE
- 8. Frequency of participant's response of the degree they are troubled with treatment symptoms, as assessed through use of the single-item European Organisation for Research and Treatment of Cancer (EORTC) Item List 46 (IL46)
- 9. Plasma concentration of divarasib at specified timepoints
- 10. Recommended dose of divarasib in combination with pembrolizumab (Cohort A) or pembrolizumab plus platinum-based chemotherapy and pemetrexed (Cohort B) based on the totality of safety, activity, and PK data
研究者
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG
研究点 (20)
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