An Open Label, Multicenter, Dose Escalation, Phase 1 Study to Evaluate Safety/Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti Tumor Activity of RO7247669, a PD1-LAG3 Bispecific Antibody, in Patients With Advanced and/or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 170
- 试验地点
- 50
- 主要终点
- Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
This is a first-in-human, open-label, multicenter, Phase I multiple-ascending dose (MAD) study of RO7247669, an anti PD-1 (programmed death-1) and LAG-3 (Lymphocyte-activation gene 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. This study aims to establish the maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D) based on the safety, tolerability, pharmacokinetic (PK) and/or pharmacodynamic (PD) profile of RO7247669, and to evaluate preliminary anti-tumor activity in participants with solid tumors. An expansion part of the study is planned to enroll tumor-specific cohorts to evaluate anti-tumor activity of the MTD and/or RP2D of RO7247669 and to confirm safety and tolerability in participants with selected tumor types.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient
- •Eastern Cooperative Oncology Group Performance Status 0-1
- •Fresh biopsies may be required
- •Women of childbearing potential and male participants must agree to remain abstinent or use contraceptive methods as defined by the protocol
- •Additional Specific Inclusion Criteria for Participants with Melanoma
- •Histologically confirmed, unresectable stage III or stage IV melanoma
- •Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling in the study
- •Prior treatment with an approved anti-PD-1 or anti-PD-L1 agent
- •Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously Received Treatment for Metastatic Disease
- •Participants with histologically confirmed advanced non-small cell lung cancer
- •Not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling in the study
- •Previously treated with approved PD-L1/PD-1 inhibitors
- •Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening
- •Additional Specific Inclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma
- •Participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus
- •Participants who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling in the study
- •Additional Specific Inclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously did not Receive Treatment for Metastatic Disease
- •Participants with histologically confirmed advanced non-small cell lung cancer
- •Tumor PD-L1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening
排除标准
- •Pregnancy, lactation, or breastfeeding
- •Known hypersensitivity to any of the components of RO7247669
- •Active or untreated central nervous system (CNS) metastases
- •An active second malignancy
- •Evidence of concomitant diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
- •Positive HIV, hepatitis B, or hepatitis C test result
- •Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection
- •Vaccination with live vaccines within 28 days prior to Cycle 1 Day 1
- •Treatment with oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
- •Active or history of autoimmune disease or immune deficiency
- •Prior treatment with adoptive cell therapies, such as CAR-T therapies
- •Concurrent therapy with any other investigational drug < 28 days or 5 half-lives of the drug, whichever is shorter, prior to the first RO7247669 administration
- •Regular immunosuppressive therapy
- •Radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy
- •Prior treatment with a lymphocyte activation gene-3 (LAG-3) inhibitor
- •Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously Received Treatment for Metastatic Disease
- •Participants with the following muations, rearrangements, translocations are not eligible: EGFR, ALK, ROS1, BRAFV600E, and NTRK
- •Additional Specific Exclusion Criteria for Participants with Esophageal Squamous Cell Carcinoma
- •Prior therapy with any immunomodulatory agents
- •Additional Specific Exclusion Criteria for Participants with Non-Small Cell Lung Cancer who Previously did not Receive Treatment for Metastatic Disease
- •Prior therapy for metastatic disease is not permitted
- •Neo-adjuvant anti-PD-1 or anti-PD-L1 therapy is not allowed
研究组 & 干预措施
Part B: Tumor Specific Expansion Cohorts
Participants with selected solid tumor indications will receive RO7247669 at a dose derived from Part A until disease progression, unacceptable drug toxicity, or withdrawal of consent, for up to 24 months.
干预措施: RO7247669 (Drug)
Part A: Single-Agent Dose Escalation
Participants will receive RO7247669 every 2 weeks (Q2W) or every 3 weeks (Q3W) up to the maximum tolerated dose (MTD) until disease progression, unacceptable drug toxicity, or withdrawal of consent, for up to 24 months.
干预措施: RO7247669 (Drug)
结局指标
主要结局
Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
时间窗: Days 1-21 (Q2W dosing) or Days 1-28 (Q3W dosing) of Cycle 1
Part A: Percentage of Participants with Adverse Events
时间窗: Baseline through the end of study (up to 24 months)
Part B: Duration of Response (DOR)
时间窗: Up to 24 months
Part B: Disease Control Rate (DCR), Defined as ORR + Stable Disease Rate (SDR)
时间窗: Up to 24 months
Part B: Progression-free Survival (PFS), Defined as the Time from the First Study Treatment to the First Occurrence of Progression per Investigator Assessment or Death from any Cause, Whichever Occurs First
时间窗: Up to 24 months
Part B: Objective Response Rate (ORR)
时间窗: Up to 24 months
次要结局
- Parts A and B: Clearance (CL) of RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Parts A and B: Area Under the Curve (AUC) of RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Part A: ORR(At pre-defined intervals from initial dose up to 24 months)
- Part A: DCR(At pre-defined intervals from initial dose up to 24 months)
- Part A: DOR(At pre-defined intervals from initial dose up to 24 months)
- Parts A and B: Time of Maximum Concentration (Tmax) of RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Parts A and B: Half-Life (T1/2) of RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Parts A and B: Percentage of Participants with Anti-Drug Antibodies (ADA) to RO7247669(Day 1 of each Cycle, starting with Cycle 1, through final study visit (up to 24 months))
- Part B: Change from Baseline in T-Cell Activity(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Part A: PFS(At pre-defined intervals from initial dose up to 24 months)
- Part B: Percentage of Participants with Adverse Events(Baseline through the end of study (up to 24 months))
- Parts A and B: Maximum Concentration (Cmax) of RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Parts A and B: Volume of Distribution at Steady State (Vss) of RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))
- Part A: Percentage of Receptors Occupied by RO7247669(At pre-defined intervals from Day 1 of Cycle 1 through final study visit (up to 24 months))