Symbiotic-GI-13: 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.

Official title

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

Overview

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.

Interventions

• Biological PF-08634404
  Solution for infusion
• Biological Ipilimumab
  Solution for infusion

Primary outcome measures

• Number of Participants With Adverse Events [Time frame: Through end of study and up to approximately 24 months]
• Phase 1b: Number of participants with Dose limiting toxicities (DLT) [Time frame: Through 90 days after the last dose of study intervention; Approximately 24 months]
• Phase 2: Confirmed Overall Response Rate (ORR) using RECIST 1.1 as assessed by investigator [Time frame: Approximately 24 months]
• Phase 2: Recommended dose of PF-08634404 in combination with ipilimumab [Time frame: Approximately 24 months]

Secondary outcome measures (7)

• Phase 1b: Confirmed Objective Response Rate (ORR) using RECIST 1.1 as assessed by investigator [Time frame: Approximately 24 months]
• Duration of Response (DOR) per RECIST 1.1 by investigator [Time frame: Approximately 24 months]
• Progression Free Survival (PFS) per RECIST 1.1 by investigator [Time frame: Approximately 24 months]
• Overall Survival (OS) [Time frame: Approximately 24 months]
• Number of Participants With Clinical Laboratory Abnormalities [Time frame: 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 [Time frame: Up to 24 months]
• Incidence of antidrug antibody against PF-08634404 [Time frame: Up to 24 months]

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 37 centers

• Keck Hospital of USC — Los Angeles
• Los Angeles General Medical Center — Los Angeles
• USC/Norris Comprehensive Cancer Center / Investigational Drug Services — Los Angeles
• USC/Norris Comprehensive Cancer Center — Los Angeles
• Keck Medical Center of USC Pasadena — Pasadena
• Moffitt Cancer Center at Speros — Land O' Lakes
• Moffitt Cancer Center at SouthShore — Ruskin
• Moffitt Cancer Center - International Plaza — Tampa
• … and 29 more centers

Japan · 4 centers

• Aichi Cancer Center — Nagoya
• National Cancer Center Hospital East — Kashiwa
• Kindai University Hospital- Osaka Medical Campus — Sakai
• National Hospital Organization Kyushu Cancer Center — Fukuoka

Puerto Rico · 4 centers

• Pan American Center for Oncology Trials, LLC - Dorado Office — Dorado
• Pan American Center for Oncology Trials, LLC - Mayaguez Office — Mayagüez
• Pan American Center for Oncology Trials, LLC - Ponce Office — Ponce
• Pan American Center for Oncology Trials, LLC — San Juan

Taiwan · 4 centers

• Taichung Veterans General Hospital — Taichung
• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

Identifiers

NCT: NCT07227012 · C6461013 · 2025-523525-17-00 · Symbiotic-GI-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗