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

A Randomized Phase 2 Trial of Atezolizumab and Bevacizumab in Combination With SRF388 or Placebo in Patients With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: SRF388; Drug: Atezolizumab; Drug: Bevacizumab; Drug: Placebo

Detailed Description

This is a Phase 2 trial designed to evaluate the efficacy and safety of SRF388 in combination with atezolizumab plus bevacizumab (Arm A) compared to placebo in combination with atezolizumab plus bevacizumab (Arm B) in patients with first-line advanced or metastatic HCC.

After a Lead-In Phase of up to 30 patients who will receive open-label SRF388 + atezolizumab + bevacizumab, the blinded Randomized Phase will randomize approximately 104 patients with a 1:1 allocation to Arm A or Arm B and stratified by geographic region (Asia excluding Japan vs. rest of world) and Barcelona Clinic Liver Cancer (BCLC) stage (B or C).

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hillary O'Kelly, MPH; Phone Number: +1-805-551-1699; Email: hokelly@coherus.com

Study Locations

• Australia
  • Melbourne, Australia
    • Royal Melbourne Hospital
  • Melbourne, Australia, 3004
    • The Alfred Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 705-718
    • Daegu Catholic University Medical Center (DCUMC)
  • Gyeonggi-do, Korea, Republic of, 443-721
    • Ajou University Hospital
  • Gyeonggi-do, Korea, Republic of, 463-712
    • CHA University - Bundang CHA General Hospital (CHA Bundang Medical Center)
  • Jeollanam-do, Korea, Republic of, 58128
    • Chonnam National University (CNU) - Chonnam National University Hwasun Hospital (CNUHH)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 135-720
    • Gangnam Severance Hospital - Cancer Hospital
  • Seoul, Korea, Republic of, 136-705
    • Korea University Medical Center - Korea University Anam Hospital
  • Seoul, Korea, Republic of, 138-736
    • University of Ulsan College of Medicine - Asan Medical Center (AMC)
  • Seoul, Korea, Republic of, 156-707
    • Seoul National University Hospital (SNUH) - SMG-SNU Boramae Medical Center
  • Gyeonggi-Do
    • Seongnamsi Bundang, Gyeonggi-Do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-Do, Korea, Republic of, 442-723
      • The Catholic University of Korea - St. Vincent's Hospital
  • Gyeongsangnam-do
    • Yangsan-si, Gyeongsangnam-do, Korea, Republic of, 50612
      • Pusan National University Yangsan Hospital
• Taiwan
  • Hualien City, Taiwan, 970
    • Buddhist Tzu Chi General Hospital - Hualien Tzu Chi Medical Center
  • Kao-Hsiung, Taiwan, 82445
    • E-Da Cancer Hospital
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University - Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei City, Taiwan, 10002
    • National Taiwan University Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center - North Campus
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90033
      • University of Southern California - Norris Comprehensive Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Health Science Center - Gainesville
    • Miami, Florida, United States, 33136
      • University of Miami, Sylvester Comprehensive Cancer Center
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Louisville VA Medical Center - Robley Rex VA Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Veterans Affairs Ann Arbor Healthcare System
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System (UMHS)
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New York
    • New York, New York, United States, 10010
      • Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center
    • New York, New York, United States, 10016
      • NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI))
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center - Stephenson Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute - Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute - Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Abbreviated Inclusion Criteria:

• ≥ 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

Abbreviated Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lead-In; 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; SRF388 will be administered by intravenous injection (IV); Drug: Atezolizumab; Azezolizumab will be administered by IV; Other Names: Tecentriq; Drug: Bevacizumab; Bevacizumab will be administered by IV; Other Names: Avastin
Experimental: Arm A: SRF388 in Combination with atezolizumab plus bevacizumab; Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab.	Drug: SRF388; SRF388 will be administered by intravenous injection (IV); Drug: Atezolizumab; Azezolizumab will be administered by IV; Other Names: Tecentriq; Drug: Bevacizumab; Bevacizumab will be administered by IV; Other Names: Avastin
Experimental: Arm B: Placebo in combination with atezolizumab plus bevacizumab; Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.	Drug: Atezolizumab; Azezolizumab will be administered by IV; Other Names: Tecentriq; Drug: Bevacizumab; Bevacizumab will be administered by IV; Other Names: Avastin; Drug: Placebo; Placebo will be administered by IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) according to RECIST v1.1	Progression Free Survival (PFS) according to RECIST v1.1 (Lead-In Phase).	Up to 2 years
PFS according to HCC modified RECIST (mRECIST)	PFS according to HCC mRECIST.	Up to 2 years
Objective Response Rate (ORR) according to RECIST v1.1	ORR according to RECIST v1.1.	Up to 2 years
ORR according to HCC mRECIST	ORR according to HCC mRECIST.	Up to 2 years
Duration of Response (DoR) according to RECIST 1.1	DoR will be determined according to RECIST v1.1.	Up to 2 years
Duration of Response (DoR) according to HCC mRECIST	DoR will be determined according to HCC mRECIST.	Up to 2 years
Disease Control Rate (DCR)	DCR will measure the proportion of patients who experience best overall response of complete response (CR), partial response (PR), or stable disease (SD).	Up to 2 years
Time to Progression (TTP) according to RECIST v1.1	TTP according to RECIST v1.1.	Up to 2 years
TTP according to mRECIST	TTP according to HCC mRECIST.	Up to 2 years
Overall Survival (OS)	OS, defined as time from study drug initiation (Lead-In) or randomization to death from any cause.	Up to 2 years
Time to Response according to RECIST v1.1	Time to response will be evaluated according to RECIST v1.1	Up to 2 years
Time to Response according to HCC mRECIST	Time to response will be evaluated according to HCC mRECIST	Up to 2 years
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 (Randomized Phase).	Up to 2 years
Incidence of SRF388 Antidrug Antibodies (ADAs)	Percentage of patients who develop ADAs to SRF388.	Up to 2 years
Incidence of atezolizumab ADAs	Percentage of patients who develop ADAs to atezolizumab.	Up to 2 years
Maximum observed serum concentration (Cmax) of SRF388	Serum samples will be collected and analyzed to assess the Cmax of SRF388.	Up to 2 years
Time of maximum observed serum concentration (tmax) of SRF388	Serum samples will be collected and analyzed to assess the (tmax) of SRF388.	Up to 2 years
Area under the serum concentration-time curve from time zero to the last quantifiable time point (AUC0-last)	Serum samples will be collected and analyzed to assess AUC0-last of SRF388.	Up to 2 years
Terminal elimination half-life (t1/2)	Serum samples will be collected and analyzed to assess the t1/2 of SRF388.	Up to 2 years
Serum concentrations of atezolizumab	Serum samples of atezolizumab will be collected to assess maintenance concentrations of atezolizumab	Up to 2 years

Collaborators and Investigators

• Sponsor: Coherus Biosciences, Inc.
• Investigators: Study Chair: Vienna Reichert, PhD, Coherus Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: safety; immunotherapy; cancer; bevacizumab; hepatocellular carcinoma; efficacy; Avastin; atezolizumab; immuno-oncology; Phase 2; liver cancer; Tecentriq; SRF388; IL-27
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Bevacizumab; Atezolizumab
• Other Study ID Numbers: SRF388-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No