A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0919 Administered With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 158
- 试验地点
- 18
- 主要终点
- Percentage of Participants With Dose-limiting Toxicities (DLTs)
研究概览
简要总结
This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy at least 12 weeks
- •Adequate hematologic and end organ function
- •Negative pregnancy test and willingness to utilize contraception among women of childbearing potential
- •Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1
- •Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care
- •For the expansion stage, histologically confirmed renal cell cancer (RCC), urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma (HNSCC), gastric cancer, ovarian cancer, cervical cancer, endometrial cancer, or Merkel cell cancer
- •For the expansion stage, evaluable for PD-L1 expression
- •Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled
排除标准
- •Significant cardiovascular or liver disease
- •Major surgery within 28 days of study drug
- •Any anti-cancer therapy within 3 weeks of study drug
- •Malabsorption syndrome or poor upper gastrointestinal integrity
- •Primary central nervous system (CNS) malignancy or active metastases within 5 years
- •Uncontrolled tumor pain
- •Autoimmune disease other than stable hypothyroidism or vitiligo
- •Human immunodeficiency virus (HIV), active hepatitis B or C, or tuberculosis
- •Signs/symptoms of infection, or use of antibiotics within 2 weeks of study drug
- •Live attenuated vaccine within 4 weeks of study drug
- •Known history or predisposition to QT interval prolongation
- •Prior cancer immunotherapy, specifically indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) inhibitors, T-cell costimulatory receptor agonist antibodies, or checkpoint inhibitors among certain participants
研究组 & 干预措施
Anti-PD-1/PD-L1 Relapsed Cohort I
Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: Atezolizumab (Drug)
Anti-PD-1/PD-L1 Relapsed Cohort I
Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: GDC-0919 (Drug)
Anti-PD-1/PD-L1 Relapsed Cohort II
Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: Atezolizumab (Drug)
Anti-PD-1/PD-L1 Relapsed Cohort II
Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: GDC-0919 (Drug)
Biopsy Cohort A
Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: Atezolizumab (Drug)
Biopsy Cohort A
Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: GDC-0919 (Drug)
Biopsy Cohort B
Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: Atezolizumab (Drug)
Biopsy Cohort B
Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: GDC-0919 (Drug)
Dose-Escalation Cohort(s)
Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage.
干预措施: Atezolizumab (Drug)
Dose-Escalation Cohort(s)
Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage.
干预措施: GDC-0919 (Drug)
Expansion Cohorts
Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: Atezolizumab (Drug)
Expansion Cohorts
Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.
干预措施: GDC-0919 (Drug)
结局指标
主要结局
Percentage of Participants With Dose-limiting Toxicities (DLTs)
时间窗: From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
Percentage of Participants With Adverse Events
时间窗: From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years)
次要结局
- Number of Treatment Cycles Received With GDC-0919 and Atezolizumab(From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years))
- Recommended Phase II Dose (RP2D) for GDC-0919(From Day -1 to 21 of Cycle 1 (each cycle is 21 days))
- Dose Intensity of GDC-0919 and Atezolizumab(From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years))
- Plasma Minimum Concentration (Cmin) of GDC-0919(Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8)
- Time to Maximum Concentration (Tmax) of GDC-0919(Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2)
- Serum Cmax of Atezolizumab(Post-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years))
- Maximum Tolerated Dose (MTD) of GDC-0919(From Day -1 to 21 of Cycle 1 (each cycle is 21 days))
- Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator(From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years))
- Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor(From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years))
- Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as Determined by the Investigator(From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years))
- Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab(Pre-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years))
- Plasma Maximum Concentration (Cmax) of GDC-0919(Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2)
- Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919(Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8)
- Serum Cmin of Atezolizumab(Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years))
- Duration of Objective Response According to Modified RECIST as Determined by the Sponsor(From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years))