A Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Patients With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 6
- 主要终点
- Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
研究概览
简要总结
The main purpose of the study is to evaluate the safety of GDC-1971 in combination with either osimertinib or cetuximab. The study consists of a dose-finding stage followed by an expansion stage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Evaluable or measurable disease per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy of ≥12 weeks
- •Adequate hematologic and organ function within 14 days prior to initiation of study Inclusion Criteria for Non-Small Cell Lung Cancer Cohorts
- •Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the lung that has progressed on/after prior treatment with third-generation epidermal growth factor receptor (EGFR) inhibitor (e.g., osimertinib)
- •Positive for an EGFR exon 19 deletion or exon 21 L858R mutation
- •Negative for acquired on-target EGFR alterations Inclusion Criteria for Colorectal Cancer Cohorts
- •Histologically confirmed metastatic adenocarcinoma of the colon or rectum that has progressed on/after prior treatment with an EGFR inhibitor (e.g., cetuximab or panitumumab)
- •Negative for kirsten rat sarcoma viral oncogene homolog (KRAS) alterations
- •Negative for neuroblastoma RAS viral oncogene homolog (NRAS) alterations
- •Negative for proto-oncogene B-Raf (BRAF) V600E alterations
- •In lieu of a fresh pre-treatment biopsy, a recently obtained biopsy performed after completion of osimertinib therapy will be acceptable
排除标准
- •Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 3 weeks or 5 drug elimination half-lives, whichever is shorter, prior to initiation of study treatment
- •Treatment with endocrine therapy within 2 weeks prior to initiation of study drug, except for hormonal therapy with gonadotropin-releasing hormone agonists or antagonists for endocrine-sensitive cancers
- •Significant traumatic injury or major surgical procedure within 4 weeks prior to Cycle 1, Day 1
- •Positive hepatitis C virus (HCV) antibody test at screening
- •Positive hepatitis B surface antigen (HBsAg) test at screening
- •Known HIV infection
- •Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
- •Uncontrolled hypercalcemia
- •Substance abuse, as determined by the investigator, within 12 months prior to screening
- •Poor peripheral venous access
- •Inability or unwillingness to swallow pills
- •Malabsorption syndrome or other condition that would interfere with enteral absorption Chronic diarrhea, short bowel syndrome, or significant upper GI surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or any active bowel inflammation (including diverticulitis)
- •Serious infection within 4 weeks prior to screening
- •History of malignancy within 3 years prior to screening
- •Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
- •Leptomeningeal disease or carcinomatous meningitis
- •History or presence of an abnormal electrocardiogram (ECG) that is deemed clinically significant by the investigator (e.g., complete left bundle branch block, second- or third-degree atrioventricular heart block) or evidence of prior myocardial infarction
- •Left ventricular ejection fraction (LVEF) less than the institutional lower limit of normal (LLN) or <50%
- •History or evidence of ophthalmic disease
- •History of or active clinically significant cardiovascular dysfunction
- •History of pulmonary firbrosis, organizing pneumonia, or pneumonitis
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)
Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at an assigned dose, orally, once daily (QD), on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 milligrams (mg), orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.
干预措施: GDC-1971 (Drug)
Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)
Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at an assigned dose, orally, once daily (QD), on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 milligrams (mg), orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.
干预措施: Osimertinib (Drug)
Dose-Finding Stage: Colorectal Cancer (CRC)
Participants with metastatic CRC will receive GDC-1971, at an assigned dose, orally, QD, on Days 1 to 28 days of each 28-day cycle in combination with cetuximab, 500 milligrams per square meter (mg/m^2), given by IV infusion on Days 1 and 15 of each cycle, until disease progression or unacceptable toxicity.
干预措施: GDC-1971 (Drug)
Dose-Finding Stage: Colorectal Cancer (CRC)
Participants with metastatic CRC will receive GDC-1971, at an assigned dose, orally, QD, on Days 1 to 28 days of each 28-day cycle in combination with cetuximab, 500 milligrams per square meter (mg/m^2), given by IV infusion on Days 1 and 15 of each cycle, until disease progression or unacceptable toxicity.
干预措施: Cetuximab (Drug)
Dose Expansion Stage: NSCLC
Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 mg, orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.
干预措施: GDC-1971 (Drug)
Dose Expansion Stage: NSCLC
Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 mg, orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.
干预措施: Osimertinib (Drug)
Dose Expansion Stage: CRC
Participants with metastatic CRC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with cetuximab, 500 mg/m^2, given by IV infusion on Days 1 and 15 of each cycle until disease progression or unacceptable toxicity.
干预措施: GDC-1971 (Drug)
Dose Expansion Stage: CRC
Participants with metastatic CRC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with cetuximab, 500 mg/m^2, given by IV infusion on Days 1 and 15 of each cycle until disease progression or unacceptable toxicity.
干预措施: Cetuximab (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
时间窗: Up to approximately 41 months
Number of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Day 1 through Day 28 of Cycle 1 (1cycle= 28 days)
次要结局
- Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).(Up to approximately 41 months)
- Plasma Concentration of GDC-1971(Up to approximately 41 months)
- Plasma Concentration of Osimertinib(Up to approximately 41 months)
- Progression-Free Survival (PFS) After Enrollment as Determined by Investigator According to RECIST v1.1(Up to approximately 41 months)
- Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1(Up to approximately 41 months)