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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05359861
• Other study ID #: SRF388-201
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: April 12, 2022
• Est. completion date: March 2025

Study information

• Verified date: February 2024
• Source: Coherus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 134
• Est. completion date: March 2025
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• SRF388
SRF388 will be administered by intravenous injection (IV)
• Atezolizumab
Azezolizumab will be administered by IV
• Bevacizumab
Bevacizumab will be administered by IV
• Placebo
Placebo will be administered by IV

Locations

Country	Name	City	State
Australia	Royal Melbourne Hospital	Melbourne
Australia	The Alfred Hospital	Melbourne
Korea, Republic of	Daegu Catholic University Medical Center (DCUMC)	Daegu
Korea, Republic of	Ajou University Hospital	Gyeonggi-do
Korea, Republic of	CHA University - Bundang CHA General Hospital (CHA Bundang Medical Center)	Gyeonggi-do
Korea, Republic of	Chonnam National University (CNU) - Chonnam National University Hwasun Hospital (CNUHH)	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnamsi Bundang	Gyeonggi-Do
Korea, Republic of	Gangnam Severance Hospital - Cancer Hospital	Seoul
Korea, Republic of	Korea University Medical Center - Korea University Anam Hospital	Seoul
Korea, Republic of	Seoul National University Hospital (SNUH) - SMG-SNU Boramae Medical Center	Seoul
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	University of Ulsan College of Medicine - Asan Medical Center (AMC)	Seoul
Korea, Republic of	The Catholic University of Korea - St. Vincent's Hospital	Suwon-si	Gyeonggi-Do
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan-si	Gyeongsangnam-do
Taiwan	Buddhist Tzu Chi General Hospital - Hualien Tzu Chi Medical Center	Hualien City
Taiwan	E-Da Cancer Hospital	Kao-Hsiung
Taiwan	Kaohsiung Medical University - Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei City
United States	University of Michigan Health System (UMHS)	Ann Arbor	Michigan
United States	Veterans Affairs Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	Sarah Cannon Research Institute - Tennessee Oncology	Chattanooga	Tennessee
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	University of Southern California - Norris Comprehensive Cancer Center	Los Angeles	California
United States	Louisville VA Medical Center - Robley Rex VA Medical Center	Louisville	Kentucky
United States	University of Miami, Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI))	New York	New York
United States	Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center	New York	New York
United States	University of Oklahoma Health Sciences Center - Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Providence Portland Medical Center	Portland	Oregon
United States	University of Arizona Cancer Center - North Campus	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Coherus Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	PFS according to HCC modified RECIST (mRECIST)	PFS according to HCC mRECIST.	Up to 2 years
Secondary	Objective Response Rate (ORR) according to RECIST v1.1	ORR according to RECIST v1.1.	Up to 2 years
Secondary	ORR according to HCC mRECIST	ORR according to HCC mRECIST.	Up to 2 years
Secondary	Duration of Response (DoR) according to RECIST 1.1	DoR will be determined according to RECIST v1.1.	Up to 2 years
Secondary	Duration of Response (DoR) according to HCC mRECIST	DoR will be determined according to HCC mRECIST.	Up to 2 years
Secondary	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
Secondary	Time to Progression (TTP) according to RECIST v1.1	TTP according to RECIST v1.1.	Up to 2 years
Secondary	TTP according to mRECIST	TTP according to HCC mRECIST.	Up to 2 years
Secondary	Overall Survival (OS)	OS, defined as time from study drug initiation (Lead-In) or randomization to death from any cause.	Up to 2 years
Secondary	Time to Response according to RECIST v1.1	Time to response will be evaluated according to RECIST v1.1	Up to 2 years
Secondary	Time to Response according to HCC mRECIST	Time to response will be evaluated according to HCC mRECIST	Up to 2 years
Secondary	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
Secondary	Incidence of SRF388 Antidrug Antibodies (ADAs)	Percentage of patients who develop ADAs to SRF388.	Up to 2 years
Secondary	Incidence of atezolizumab ADAs	Percentage of patients who develop ADAs to atezolizumab.	Up to 2 years
Secondary	Maximum observed serum concentration (Cmax) of SRF388	Serum samples will be collected and analyzed to assess the Cmax of SRF388.	Up to 2 years
Secondary	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
Secondary	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
Secondary	Terminal elimination half-life (t1/2)	Serum samples will be collected and analyzed to assess the t1/2 of SRF388.	Up to 2 years
Secondary	Serum concentrations of atezolizumab	Serum samples of atezolizumab will be collected to assess maintenance concentrations of atezolizumab	Up to 2 years