Clinical trial NCT05359861: Trial of Atezolizumab and Bevacizumab With SRF388 or Placebo in Patients With Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Phase 2
SRF388
IL-27
safety
efficacy
immunotherapy
cancer
immuno-oncology
liver cancer
hepatocellular carcinoma
atezolizumab
Tecentriq
bevacizumab
Avastin
Lead sponsor: Coherus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2022-05-04
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher
timeFrame: Up to 2 years
measure: Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS) according to RECIST v1.1
timeFrame: Up to 2 years
measure: PFS according to HCC modified RECIST (mRECIST)
timeFrame: Up to 2 years
measure: Objective Response Rate (ORR) according to RECIST v1.1
timeFrame: Up to 2 years
measure: ORR according to HCC mRECIST
timeFrame: Up to 2 years
measure: Duration of Response (DoR) according to RECIST 1.1
timeFrame: Up to 2 years
measure: Duration of Response (DoR) according to HCC mRECIST
timeFrame: Up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Time to Progression (TTP) according to RECIST v1.1
timeFrame: Up to 2 years
measure: TTP according to mRECIST
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Time to Response according to RECIST v1.1
timeFrame: Up to 2 years
measure: Time to Response according to HCC mRECIST
timeFrame: Up to 2 years
measure: Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher
timeFrame: Up to 2 years
measure: Incidence of SRF388 Antidrug Antibodies (ADAs)
timeFrame: Up to 2 years
measure: Incidence of atezolizumab ADAs
timeFrame: Up to 2 years
measure: Maximum observed serum concentration (Cmax) of SRF388
timeFrame: Up to 2 years
measure: Time of maximum observed serum concentration (tmax) of SRF388
timeFrame: Up to 2 years
measure: Area under the serum concentration-time curve from time zero to the last quantifiable time point (AUC0-last)
timeFrame: Up to 2 years
measure: Terminal elimination half-life (t1/2)
timeFrame: Up to 2 years
measure: Serum concentrations of atezolizumab
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center - North Campus
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of Southern California - Norris Comprehensive Cancer Center
state: California
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Louisville
country: United States
facility: Louisville VA Medical Center - Robley Rex VA Medical Center
state: Kentucky
city: Ann Arbor
country: United States
facility: Veterans Affairs Ann Arbor Healthcare System
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System (UMHS)
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: New York
country: United States
facility: Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI))
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center - Stephenson Cancer Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
city: Seongnamsi Bundang
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-Do
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea - St. Vincent's Hospital
state: Gyeonggi-Do
city: Yangsan-si
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnam-do
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center (DCUMC)
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA University - Bundang CHA General Hospital (CHA Bundang Medical Center)
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University (CNU) - Chonnam National University Hwasun Hospital (CNUHH)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital - Cancer Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Medical Center - Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: University of Ulsan College of Medicine - Asan Medical Center (AMC)
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital (SNUH) - SMG-SNU Boramae Medical Center
city: Hualien City
country: Taiwan
facility: Buddhist Tzu Chi General Hospital - Hualien Tzu Chi Medical Center
city: Kao-Hsiung
country: Taiwan
facility: E-Da Cancer Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University - Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Coherus Biosciences, Inc.
name: Koho Iizuka, MD
role: STUDY_CHAIR
References: