A Phase Ia/Ib, Open Label, Multicenter, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Activity of Enzelkitug as a Single Agent and in Combination With Checkpoint Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- Atezolizumab
- 疾病 / 适应症
- Locally Advanced or Metastatic Solid Tumors
- 发起方
- Genentech, Inc.
- 入组人数
- 450
- 试验地点
- 82
- 主要终点
- Phase Ia: Number of Participants With Dose-limiting Toxicities (DLTs)
- 状态
- 招募中
- 最后更新
- 17天前
概览
简要总结
This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of enzelkitug when administered as a single agent and in combination with atezolizumab or pembrolizumab in adult participants with locally advanced or metastatic solid tumors, including non small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, triple-negative breast cancer (TNBC), esophageal cancer, gastric cancer, cervical cancer, colorectal cancer (CRC), urothelial carcinoma (UC), clear cell renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Participants will be enrolled in 2 stages: dose escalation and dose expansion.
研究者
入排标准
入选标准
- •Life expectancy of at least 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
- •Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy
- •Tumor specimen availability
排除标准
- •Pregnant or breastfeeding or intention of becoming pregnant during the study or within 4 months after the final dose of enzelkitug, or 4 months after the final dose of pembrolizumab, or 5 months after the final dose of atezolizumab
- •Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study treatment
- •Active hepatitis B (HBV) or hepatitis C (HCV) or tuberculosis
- •Positive test for human immunodeficiency virus (HIV) infection
- •Acute or chronic active Epstein-Barr virus (EBV) infection at screening
- •Administration of a live, attenuated vaccine (e.g., FluMist) within 4 weeks before first enzelkitug infusion
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Active or history of autoimmune disease
- •Prior allogeneic stem cell or organ transplantation
研究组 & 干预措施
Phase Ib: Dose Escalation
Participants in successive cohorts will receive escalating doses of enzelkitug, as an IV infusion, in combination with a fixed dose of atezolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Atezolizumab
Phase Ib: Expansion
Participants with select solid tumors will receive a recommended dose of enzelkitug, determined in Phase Ib dose escalation phase, as an IV infusion, in combination with a fixed dose of atezolizumab or pembrolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Pembrolizumab
Phase Ib: Expansion
Participants with select solid tumors will receive a recommended dose of enzelkitug, determined in Phase Ib dose escalation phase, as an IV infusion, in combination with a fixed dose of atezolizumab or pembrolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Atezolizumab
Phase Ia: Dose Escalation
Participants in successive cohorts will receive escalating doses of enzelkitug, as an intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Enzelkitug
Phase Ia: Expansion
Participants with select solid tumors will receive a recommended dose of enzelkitug, determined in Phase Ia dose escalation phase as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Enzelkitug
Phase Ib: Dose Escalation
Participants in successive cohorts will receive escalating doses of enzelkitug, as an IV infusion, in combination with a fixed dose of atezolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Enzelkitug
Phase Ib: Expansion
Participants with select solid tumors will receive a recommended dose of enzelkitug, determined in Phase Ib dose escalation phase, as an IV infusion, in combination with a fixed dose of atezolizumab or pembrolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity.
干预措施: Enzelkitug
结局指标
主要结局
Phase Ia: Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment) (1 Cycle=21 days)
Phase Ib: Number of Participants With DLTs
时间窗: From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment) (1 Cycle=21 days)
Phase Ia: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to approximately 52 months
Phase Ib: Number of Participants With TEAEs
时间窗: Up to approximately 52 months
Phase Ia: Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment)
Phase Ib: Number of Participants with DLTs
时间窗: From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment)
Phase Ia: Number of Participants with Treatment Emergent Adverse Events
时间窗: Up to approximately 5 years
Phase Ib: Number of Participants with Treatment Emergent Adverse Events
时间窗: Up to approximately 5 years
次要结局
- Phase Ia and Phase Ib: Maximum Serum Concentration (Cmax) of Enzelkitug(From Cycle 1 (each cycle is 21 days) Day 1, and at multiple timepoints up to each follow-up visits (up to approximately 52 months))
- Phase Ia and Phase Ib: Objective Response Rate (ORR)(From Cycle 1(each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 52 months))
- Phase Ia and Phase Ib: Duration of Response (DOR)(From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 52 months))
- Phase Ia and Phase Ib: Progression-free Survival (PFS)(From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 52 months))
- Phase Ia and Phase Ib: Percentage of Participants With Anti-drug Antibody (ADA) to Enzelkitug(From Cycle 1 (each cycle is 21 days) Day 1, and at multiple timepoints up to treatment discontinuation (up to approximately 52 months))
- Phase Ia and Phase Ib: Maximum Serum Concentration (Cmax) of RO7502175(From Cycle 1 (each cycle is 21 days) Day1 and at multiple timepoints up to each follow-up visits (up to approximately 5 years))
- Phase Ia and Phase Ib: Objective Response Rate (ORR)(From Cycle 1(each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 5 years))
- Phase Ia and Phase Ib: Duration of Response (DOR)(From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 5 years))
- Phase Ia and Phase Ib: Progression Free Survival (PFS)(From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 5 years))
- Phase Ia and Phase Ib: Percentage of Participants With Anti-Drug Antibody (ADA) to RO7502175(From Cycle 1 (each cycle is 21 days) Day 1 and at multiple timepoints up to treatment discontinuation (up to approximately 5 years))