AN INTERVENTIONAL OPEN-LABEL PHASE 1B/2 STUDY TO EVALUATE SAFETY, PHARMACOKINETICS, AND PRELIMINARY EFFICACY OF PF-08634404 AS MONOTHERAPY AND COMBINATION THERAPY IN ADULT PARTICIPANTS WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC HEPATOCELLULAR CARCINOMA
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 138
- 试验地点
- 59
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
The purpose of this study is to learn about the effects of study medicine (PF-08634404) when given alone or with another antibody (ipilimumab) for the treatment of a type of liver cancer called hepatocellular carcinoma (HCC) that is either locally advanced (spread to nearby tissues) or has spread to other parts of the body.
To join the study, participants must meet the following conditions:
- Be 18 years or older.
- Have locally advanced or metastatic HCC.
- Is not a candidate for complete surgical or loco-regional therapies.
- Have not received any whole-body treatment for HCC.
Participants will receive PF-08634404 either alone or in combination with ipilimumab. The medicine will be given through intravenous (IV) infusions, which means it will be administered directly into a vein. All treatments will take place at clinical trial sites, where trained medical staff will monitor participants during and after each visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •18 years of age or older at screening.
- •Locally advanced or metastatic HCC with diagnosis confirmed by histology/cytology or clinically by AASLD criteria (for patients with cirrhosis). Participants without cirrhosis require histological confirmation of diagnosis.
- •Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and/or locoregional therapies.
- •At least 1 measurable (as defined by RECIST 1.1 per investigator) and untreated lesion.
- •Adequate hepatic, liver, and renal function
- •No prior systemic therapy for HCC.
- •ECOG performance status 0 or 1
- •Child-Pugh Class A
排除标准
- •Moderate or severe ascites.
- •History of hepatic encephalopathy.
- •Participants with known active CNS lesions, including leptomeningeal metastasis, brainstem, meningeal, or spinal cord metastases or compression.
- •Clinically significant risk of hemorrhage or fistula.
- •Participants with any history of another malignancy within 3 years.
- •History of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •Participants with active autoimmune diseases requiring systemic treatment within the past 2 years.
- •Clinically significant cardiovascular disease within 6 months prior to the first dose.
- •Major surgery or severe trauma within 4 weeks prior to the first dose or planned major surgery during the study.
- •History of severe bleeding tendency or coagulation dysfunction.
- •History of severe ulcers, unhealed wounds, gastrointestinal perforation, abdominal fistula, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding, including bleeding event due to esophageal and/or gastric varices, within 6 months prior to the first dose.
- •Participants with acute, chronic or symptomatic infections.
- •Participants with history of immunodeficiency.
研究组 & 干预措施
Phase 2
Participants will be randomized to receive either PF-08634404 monotherapy or PF-08634404 combined with ipilimumab.
干预措施: PF-08634404 (Biological)
Phase 2
Participants will be randomized to receive either PF-08634404 monotherapy or PF-08634404 combined with ipilimumab.
干预措施: Ipilimumab (Biological)
Phase 1b
Participants will be allocated to sequential dose levels of PF-08634404 and ipilimumab.
干预措施: PF-08634404 (Biological)
Phase 1b
Participants will be allocated to sequential dose levels of PF-08634404 and ipilimumab.
干预措施: Ipilimumab (Biological)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Through end of study and up to approximately 24 months
Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study intervention.
Phase 1b: Number of participants with Dose limiting toxicities (DLT)
时间窗: Through 90 days after the last dose of study intervention; Approximately 24 months
DLTs are a predefined set of adverse events that are at least possibly related to any or all of the study interventions. The number of participants who experienced DLTs during the DLT observation period.
Phase 2: Confirmed Overall Response Rate (ORR) using RECIST 1.1 as assessed by investigator
时间窗: Approximately 24 months
ORR is the proportion of participants with a best overall response (BOR) of confirmed CR or confirmed PR per RECIST 1.1 by investigator.
Phase 2: Recommended dose of PF-08634404 in combination with ipilimumab
时间窗: Approximately 24 months
The doses of PF-08634404 and ipilimumab selected to be used in combination based on safety, tolerability, pharmacokinetics, and initial anti-tumor efficacy from Phase 2.
次要结局
- Phase 1b: Confirmed Objective Response Rate (ORR) using RECIST 1.1 as assessed by investigator(Approximately 24 months)
- Duration of Response (DOR) per RECIST 1.1 by investigator(Approximately 24 months)
- Progression Free Survival (PFS) per RECIST 1.1 by investigator(Approximately 24 months)
- Overall Survival (OS)(Approximately 24 months)
- Number of Participants With Clinical Laboratory Abnormalities(Time from the date of first dose of study intervention through 30-37 days after last dose of study intervention (assessed up to approximately 24 months))
- Pharmacokinetics (PK): Serum concentrations of PF-08634404(Up to 24 months)
- Incidence of antidrug antibody against PF-08634404(Up to 24 months)