A Study to Learn About Study Medicine Called PF-08634404 as a Single Treatment and Combination Treatment in Adult Participants With a Liver Cancer Called Hepatocellular Carcinoma, That is Too Advanced to be Removed by Surgery and May Have Spread to Other Parts of the Body.
- Conditions
- Carcinoma, HepatocellularHepatocellular CancerHepatocellular CarcinomaUnresectable Hepatocellular CarcinomaLiver NeoplasmsAdvanced Hepatocellular CarcinomaMetastatic Hepatocellular Carcinoma
- Interventions
- Biological: PF-08634404
- Registration Number
- NCT07227012
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 138
- 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
Key
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1b PF-08634404 Participants will be allocated to sequential dose levels of PF-08634404 and ipilimumab. Phase 1b Ipilimumab Participants will be allocated to sequential dose levels of PF-08634404 and ipilimumab. Phase 2 PF-08634404 Participants will be randomized to receive either PF-08634404 monotherapy or PF-08634404 combined with ipilimumab. Phase 2 Ipilimumab Participants will be randomized to receive either PF-08634404 monotherapy or PF-08634404 combined with ipilimumab.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events 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) 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 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 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.
- Secondary Outcome Measures
Name Time Method Phase 1b: Confirmed Objective Response Rate (ORR) using RECIST 1.1 as assessed by investigator Approximately 24 months ORR is the proportion of participants with a best overall response of confirmed Complete Response (CR) or confirmed Partial Response (PR) per RECIST 1.1 by investigator.
Duration of Response (DOR) per RECIST 1.1 by investigator Approximately 24 months DOR is the time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the date of first documented disease progression per RECIST 1.1 as assessed by investigator, or death due to any cause, whichever occurs first.
Progression Free Survival (PFS) per RECIST 1.1 by investigator Approximately 24 months PFS is defined as the time from the date of first dose to the date of first documented disease progression per RECIST 1.1 as assessed by investigator, or death due to any cause, whichever occurs first.
Overall Survival (OS) Approximately 24 months OS is defined as the time from the date of first dose to the date of death due to any cause.
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) Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing
Pharmacokinetics (PK): Serum concentrations of PF-08634404 Up to 24 months Predose and/or postdose concentrations of PF-08634404 in combination with ipilimumab.
Incidence of antidrug antibody against PF-08634404 Up to 24 months To evaluate immunogenicity of PF-08634404 in combination with ipilimumab.