NCT05180422撤回1 期
A Phase I/II Study of AMG 510 in Combination With MVASI in Patients With Advanced, Unresectable or Metastatic KRAS G12C Mutant NSCLC With Asymptomatic Brain Metastasis.
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Dose Expansion
研究概览
简要总结
This is a multicenter, non-randomized, open-label, phase I/II study to evaluate the safety and tolerability of AMG 510 plus MVASI in subjects with advanced KRAS p.G12C mutant non-small cell lung cancer (NSCLC) with small, untreated brain metastases.
详细描述
Each patient is scheduled to receive AMG 510 (KRASG12C inhibitor) in combination with MVASI (vascular endothelial growth factor [VEGF] inhibitor; bevacizumab biosimilar); both drugs will be provided by the study:
AMG 510:
Continuous once daily (QD) oral dosing (Days 1-21 each cycle) with or without food.
MVASI:
Intravenous (i.v.) infusion every 21 days (i.e. Day 1 of each 21-day cycle).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- •Signed and dated written informed consent.
- •Male or female ≥ 18 years of age at the time of informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
- •As estimated by study physician, life expectancy ≥ 12 weeks.
- •Histologically proven, locally advanced, recurrent or metastatic KRAS G12C mutant non-small cell lung cancer (NSCLC), with pathological documentation of KRAS p.G12C mutation identified through DNA sequencing either in tumor tissue or blood circulating tumor DNA.
- •At least one untreated brain metastasis ≥ 5mm in diameter in any line of treatment:
- •Subjects with largest measurable intracranial lesion ≥5 mm but <10 mm may be allowed to enroll upon agreement with investigator (for patients with target lesions of ≥ 5mm but <10 mm, 1.5 mm slice thickness brain MRI is required).
- •"Untreated" refers to the lesion not being previously treated with stereotactic radiosurgery (SRS).
- •Prior treatment with whole brain radiation therapy or local surgery is permissible provided unequivocal progression in the lesion has since occurred and completion 14 days prior to study enrollment.
- •For at least 7 days prior to first dose of AMG 510 and MVASI in this study: Patient must be asymptomatic from CNS metastases and on a stable dose of corticosteroids.
- •Able to take oral medications and willing to record daily adherence to investigational product.
- •As assessed by electrocardiogram (ECG) completed ≤ 14 days before initiation of protocol treatment, the corrected QT interval (QTc) will be calculated by Fridericia's method (QTcF) - see Section 7.
- •Eligible candidates (male or female) must have the following QTcF value on baseline ECG:
- •QTcF ≤ 470 ms.
- •The average QTcF value from three (3) separate ECG tracings, each performed on the same day (ideally at least 5 minutes apart), will serve as the baseline QTcF value used to meet eligibility.
- •Adequate organ and bone marrow function resulted ≤ 14 days prior to first dose of protocol-indicated treatment:
- •Prothrombin time (PT) and partial thromboplastin time (PTT) < 1.5x institutional upper limit of normal (ULN).
- •Absolute neutrophil count (ANC) > 1500/µL.
- •Hemoglobin ≥ 9 g/dL.
- •Platelets ≥ 75,000/µL.
- •Total bilirubin ≤ 1.5x ULN; or
- •< 2x ULN in subjects with documented Gilbert's syndrome; or
- •< 3x ULN in subjects for whom the indirect bilirubin level suggests an extrahepatic source of total bilirubin elevation).
- •AST (SGOT) and ALT (SGPT) ≤ 2.5x ULN; or
- •≤ 5x ULN if liver metastases are present.
- •Serum creatinine ≤ 1.5mg/dL.
- •Women must not be breastfeeding and further agree to not breastfeed during study treatment; and for at least 1 week (7 days) after patient's final dose of AMG 510, and for at least 6 months (183 days) after patient's final dose of MVASI.
- •A woman of childbearing potential (WOCBP) - see Appendix 3 for definition of WOCBP - must have a negative serum or urine β-hCG pregnancy test (or in cases of β-hCG tumor production, may be confirmed not pregnant by uterine ultrasound during screening) within 14 days prior to receiving first dose of protocol-indicated treatment to be eligible, and must agree to follow instructions for using acceptable contraception (Appendix 3) from the time of signing consent, and until at least 6 months (183 days) after her final dose of AMG 510 and MVASI.
- •A man able to father children (see Appendix 3 for definition) who is sexually active with a WOCBP must agree to follow instructions for using acceptable contraception (Appendix 3), from the time of signing consent, and until at least 6 months (183 days) after his final dose of AMG 510 and MVASI.
排除标准
- •Patients meeting any of the following criteria will not be permitted to enter the trial:
- •Other coexisting malignancies or malignancies diagnosed within the previous 2 years are not eligible.
- •Exceptions to this include non-melanoma skin cancer, cervical cancer in-situ, well-differentiated thyroid cancer or prostate cancer.
- •Other cancers that per assessment of the principal investigator are not prognosis-limiting can be allowed after review by the principal investigator. If there is no evidence of disease for at least 3 years prior to initiating treatment in this study, patients may be eligible.
- •Prior receipt of AMG-510, other KRAS G12C inhibitors, or VEGF inhibitors for the treatment of non-small cell lung cancer.
- •Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure equivalent to New York Heart Association > Class II (see Appendix 2) or unstable (requiring hospitalization or heart catheterization) angina currently.
- •Patient on full dose, therapeutic anticoagulation for thromboembolic event, arrhythmia, or prothesis with coumadin.
- •Evidence of clinically significant hemorrhage (per study physician) in untreated CNS lesion(s) on screening MRI.
- •Major surgery within 28 days of enrollment or presence of a non-healing wound.
- •Proteinuria of greater than 1 gram per 24 hours.
- •Recent history of moderate or severe hemoptysis within 7 days (greater than 20mL of pure blood within 24 hours).
研究组 & 干预措施
Dose Expansion
Experimental
AMG 510/MVASI
干预措施: AMG 510 (Drug)
Dose Expansion
Experimental
AMG 510/MVASI
干预措施: MVASI (Drug)
结局指标
主要结局
Dose Expansion
时间窗: 18 weeks
Initiation of salvage radiation therapy to the CNS at 18 weeks (phase II component).
Dose Exploration
时间窗: 21 days
Safety and tolerability (phase I component). Dedicated surveillance and expedited reporting of Dose Limiting Toxicity (DLT) is required for 21 days after initiating protocol-indicated treatment A minimum of 6 patients will be treated at the Maximum tolerated dose on the phase I portion of the study in order to obtain sufficient toxicity data prior to proceeding to the phase II evaluation of this regimen
次要结局
- Dose Expansion(18.5 months)
研究者
研究点 (1)
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