A Study of TPST-1120 With Atezolizumab Plus Bevacizumab in Patients With Unresectable or Metastatic HCC Not Previously Treated With Systemic Therapy

NCT06680258 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: TPST-1120-301
• Study Type: interventional
• Target: 740
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to determine if TPST-1120 in combination with atezolizumab and bevacizumab helps patients to live longer compared to atezolizumab and bevacizumab alone (the standard of care treatment) in adult patients with hepatocellular carcinoma that cannot be removed by surgery or has spread outside of the liver (called metastatic). The trial also will study the safety and side effects of the drug combination compared to the standard of care treatment. Other questions the trial aims to answer include:

• visits to the clinic every 3 weeks for physical examination, labs and questions about health and symptoms
• measurement of their cancer by CT scan every 9 weeks. Trial participants can stop study treatment at any time they choose and for any reason. They also can continue to receive study treatment for as long as the treatment is controlling cancer growth and they are tolerating the drug effects.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Hepatocellular carcinoma; liver cancer; metastatic; atezolizumab; bevacizumab; advanced; unresectable; PD-L1; b-catenin; CTNNB1

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival (OS), defined as the time from randomization to death from any cause up to 60 months.

  The time from randomization to death from any cause up to 60 months.

Secondary Outcomes (1)

• Progression free survival

  The time from randomization to first occurence of disease progression or death from any cause (whichever occurs first) up to 60 months.

Study Arms (2)

Active Arm

EXPERIMENTAL

TPST-1120 600 mg by mouth (PO) twice daily (BID) with atezolizumab 1200 mg intravenously (IV) every 3 weeks (Q3W) and bevacizumab 15 mg/kg IV Q3W

Drug: TPST-1120; Biological: Atezolizumab; Biological: Bevacizumab

Control Arm

ACTIVE COMPARATOR

Placebo tablets PO BID with atezolizumab 1200 mg IV Q3W and bevacizumab 15 mg/kg IV Q3W

Biological: Atezolizumab; Biological: Bevacizumab

Interventions

TPST-1120 DRUG

TPST-1120 is an orally administered competitive antagonist of peroxisome proliferator-activated receptor α (PPARα)

Active Arm

Atezolizumab BIOLOGICAL

Atezolizumab is an IV administered biologic.

Active Arm; Control Arm

Bevacizumab BIOLOGICAL

Bevacizumab is an IV administered biologic.

Active Arm; Control Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age ≥ 18 years at the time of signing ICF
• HCC diagnosis confirmed by histology/cytology or clinically by the American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients
• a) Patients without cirrhosis require histological confirmation of diagnosis.
• Unresectable or metastatic disease not amenable to curative intent surgical and/or locoregional therapies
• a) Patients who have progressed after surgical and/or locoregional therapy for HCC are eligible.
• No prior systemic therapy (including systemic investigational agents) for HCC
• At least one measurable (per RECIST v1.1) untreated lesion
• Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1.
• Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade ≤ 1 prior to study entry, except for alopecia
• ECOG performance status of 0 or 1within 7 days prior to randomization
• Child-Pugh class A within 7 days prior to randomization
• Adequate organ and bone marrow function, as defined in protocol (obtained within 7 days prior to randomization unless otherwise specified)
• Negative human immunodeficiency virus (HIV) test at screening
• Documented virology status of hepatitis, as confirmed by screening tests for HBV and HCV a) For patients with active HBV: HBV DNA \< 500 IU/mL during screening, initiation of anti-HBV treatment at least 14 days prior to randomization and willingness to continue anti-HBV treatment during the study (per local standard of care; e.g., nucleos(t)ide analogues)

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low grade prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• Patients with symptomatic, untreated, or actively progressing central nervous system (CNS) metastases, or any history of leptomeningeal cancer, are not eligible.
• Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (\< 30 mm from the carina)
• a) Patients with vascular invasion of the portal or hepatic veins may be enrolled.
• Untreated or incompletely treated esophageal and/or gastric varices
• Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be treated with definitive therapy (e.g., banding) per local standard of care prior to study enrollment.
• Screening EGD does not need to be performed if EGD and definitive variceal treatment were previously completed no more than 6 months prior to initiation of study intervention.
• Grade ≥ 3 hemorrhage or bleeding event within 8 weeks prior to initiation of study intervention
• History of hemoptysis (≥ 2.5 mL of bright red blood per episode) within 1 month prior to initiation of study intervention
• Inadequately controlled hypertension, defined as systolic blood pressure (BP) \>150 mmHg and/or diastolic BP \> 100 mmHg, based on an average of at least 3 readings at 2 or more sessions
• a) Anti-hypertensive therapy to achieve these parameters is allowed.
• Prior history of hypertensive crisis or hypertensive encephalopathy
• History of hepatic encephalopathy
• History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study intervention

Sponsors & Collaborators

• Tempest Therapeutics: lead
• Hoffmann-La Roche: collaborator

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasm Metastasis

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Vice President, Development Operations

CONTACT

650-825-4259; TPST-1120-301@tempesttx.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2024
• First Posted: November 8, 2024
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): July 1, 2030
• Last Updated: September 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share