Trial of Atezolizumab and Bevacizumab With SRF388 or Placebo in Patients With Hepatocellular Carcinoma

NCT05359861 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: SRF388-201
• Study Type: interventional
• Target: 30
• Locations: 4 countries
• Sites: 37

Brief Summary

This is a Phase 2 trial composed of an open label Lead-In followed by a Randomized Phase designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab compared to placebo (inactive substance) in combination with atezolizumab plus bevacizumab in patients with first-line advanced or metastatic HCC.

Conditions

Hepatocellular Carcinoma

Keywords

Phase 2; SRF388; IL-27; safety; efficacy; immunotherapy; cancer; immuno-oncology; liver cancer; hepatocellular carcinoma; atezolizumab; Tecentriq; bevacizumab; Avastin

Outcome Measures

Primary Outcomes (2)

• Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher

  Summaries of AEs will be based on TEAEs. A TEAE is an AE that emerges or worsens in the period from the first dose of study drug to 30 days after the last dose of study drug (Lead-In Phase).

  Up to 2 years

• Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)

  PFS according to RECIST v1.1 will be evaluated in patients receiving SRF388 in combination with atezolizumab plus bevacizumab compared to placebo in combination with atezolizumab plus bevacizumab (Randomized Phase).

  Up to 2 years

Secondary Outcomes (20)

• Progression Free Survival (PFS) according to RECIST v1.1

  Up to 2 years

• PFS according to HCC modified RECIST (mRECIST)

  Up to 2 years

• Objective Response Rate (ORR) according to RECIST v1.1

  Up to 2 years

• ORR according to HCC mRECIST

  Up to 2 years

• Duration of Response (DoR) according to RECIST 1.1

  Up to 2 years

Study Arms (3)

Lead-In

EXPERIMENTAL

A minimum of 6 patients and up to 30 patients will be enrolled in an open-label Lead-In to assess the preliminary safety and tolerability of SRF388 with atezolizumab plus bevacizumab.

Drug: SRF388; Drug: Atezolizumab; Drug: Bevacizumab

Arm A: SRF388 in Combination with atezolizumab plus bevacizumab

EXPERIMENTAL

Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab.

Drug: SRF388; Drug: Atezolizumab; Drug: Bevacizumab

Arm B: Placebo in combination with atezolizumab plus bevacizumab

EXPERIMENTAL

Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.

Drug: Atezolizumab; Drug: Bevacizumab; Drug: Placebo

Interventions

SRF388 DRUG

SRF388 will be administered by intravenous injection (IV)

Arm A: SRF388 in Combination with atezolizumab plus bevacizumab; Lead-In

Atezolizumab DRUG

Azezolizumab will be administered by IV

Also known as: Tecentriq

Arm A: SRF388 in Combination with atezolizumab plus bevacizumab; Arm B: Placebo in combination with atezolizumab plus bevacizumab; Lead-In

Bevacizumab DRUG

Bevacizumab will be administered by IV

Also known as: Avastin

Arm A: SRF388 in Combination with atezolizumab plus bevacizumab; Arm B: Placebo in combination with atezolizumab plus bevacizumab; Lead-In

Placebo DRUG

Placebo will be administered by IV

Arm B: Placebo in combination with atezolizumab plus bevacizumab

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age on day of signing informed consent
• Unresectable locally advanced or metastatic HCC
• No prior systemic treatment for unresectable locally advanced or metastatic HCC
• BCLC Stage B or Stage C disease
• Child-Pugh Class A disease
• ≥ 1 measurable lesion per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Laboratory values indicative of adequate organ function as defined in the protocol
• Women of childbearing potential must have a negative pregnancy test within 1 week prior to first dose of study drug
• Women of childbearing potential or men with a heterosexual partner of childbearing potential or pregnant must agree to refrain from sexual intercourse or be willing to use effective methods of contraception as defined in the protocol while receiving study drug and for 6 months after the last dose of any study drug

You may not qualify if:

• Currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Previously received an anti-interleukin (IL)-27 antibody (Ab) or anti-IL-27-targeted therapy.
• Received prior systemic therapy for unresectable or metastatic disease. (Note: Prior systemic therapies administered for neoadjuvant, adjuvant, or curative intent (localized disease) are permitted if they were given \> 1 year prior to the development of recurrent or metastatic disease)
• Known fibrolamellar HCC histology, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• Moderate or severe ascites
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• History of or current hepatic encephalopathy
• Unable to undergo disease evaluation with a triphasic CT or MRI because of contrast allergy or other contraindication
• Untreated or incompletely treated varices with bleeding or high risk for bleeding.
• Symptomatic or untreated brain metastases or leptomeningeal carcinomatosis.
• Active or history of autoimmune disease or immune deficiency with some exceptions such as controlled thyroid disease, Type 1 diabetes, eczema and other minor skin disorders.
• Medical conditions requiring chronic steroid therapy (ie, \> 10 mg/day of prednisone or its equivalent) or anticipates the need for systemic immunosuppressive medications during treatment with study drug
• Known active infection with HIV
• Known infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), except for controlled active HBV or fully treated HCV infection as defined by the protocol
• Inadequately controlled arterial hypertension

Sponsors & Collaborators

• Coherus Oncology, Inc.: lead

Study Sites (37)

University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of Southern California - Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Louisville VA Medical Center - Robley Rex VA Medical Center

Louisville, Kentucky, 40206, United States

Location

Veterans Affairs Ann Arbor Healthcare System

Ann Arbor, Michigan, 48105, United States

Location

University of Michigan Health System (UMHS)

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center

New York, New York, 10010, United States

Location

NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI))

New York, New York, 10016, United States

Location

University of Oklahoma Health Sciences Center - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

St George Hospital -Kogarah

Kogarah, 2217, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Royal Melbourne Hospital

Melbourne, Australia

Location

Gold Coast Private Hospital

Southport, 4215, Australia

Location

The Catholic University of Korea - St. Vincent's Hospital

Suwon, Gyeonggi-do, 442-723, South Korea

Location

Daegu Catholic University Medical Center (DCUMC)

Daegu, 705-718, South Korea

Location

Chonnam National University (CNU) - Chonnam National University Hwasun Hospital (CNUHH)

Gwangju, 58128, South Korea

Location

Ajou University Hospital

Gyeonggi-do, 443-721, South Korea

Location

CHA University - Bundang CHA General Hospital (CHA Bundang Medical Center)

Gyeonggi-do, 463-712, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, 13620, South Korea

Location

Severance Hospital

Seoul, 03722, South Korea

Location

Gangnam Severance Hospital - Cancer Hospital

Seoul, 135-720, South Korea

Location

Korea University Medical Center - Korea University Anam Hospital

Seoul, 136-705, South Korea

Location

University of Ulsan College of Medicine - Asan Medical Center (AMC)

Seoul, 138-736, South Korea

Location

Seoul National University Hospital (SNUH) - SMG-SNU Boramae Medical Center

Seoul, 156-707, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

Buddhist Tzu Chi General Hospital - Hualien Tzu Chi Medical Center

Hualien City, 970, Taiwan

Location

Kaohsiung Medical University - Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

E-Da Cancer Hospital

Kaohsiung City, 82445, Taiwan

Location

Chang Gung Memorial Hospital - Kaohsiung Branch

Kaohsiung City, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Neoplasms; Liver Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Koho Iizuka, MD

  Coherus Oncology, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: April 14, 2022
• First Posted: May 4, 2022
• Study Start: April 12, 2022
• Primary Completion: June 30, 2025
• Study Completion: July 8, 2025
• Last Updated: March 18, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (6); US (15); AU (4); KR (12)