Trial of Atezolizumab and Bevacizumab With SRF388 or Placebo in Patients With Hepatocellular Carcinoma
- Conditions
- Interventions
- Registration Number
- NCT05359861
- Lead Sponsor
- Coherus Biosciences, Inc.
- 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.
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Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 134
- ≥ 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: SRF388 in Combination with atezolizumab plus bevacizumab SRF388 Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab. Lead-In SRF388 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. Lead-In Atezolizumab 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. Arm B: Placebo in combination with atezolizumab plus bevacizumab Placebo Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab. Lead-In Bevacizumab 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. Arm A: SRF388 in Combination with atezolizumab plus bevacizumab Atezolizumab Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab. Arm A: SRF388 in Combination with atezolizumab plus bevacizumab Bevacizumab Patients randomized to Arm A will receive SRF388 with atezolizumab plus bevacizumab. Arm B: Placebo in combination with atezolizumab plus bevacizumab Atezolizumab Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab. Arm B: Placebo in combination with atezolizumab plus bevacizumab Bevacizumab Patients randomized to Arm B will receive placebo with atezolizumab plus bevacizumab.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) Up to 2 years 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).
Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher Up to 2 years 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).
- Secondary Outcome Measures
Name Time Method Duration of Response (DoR) according to RECIST 1.1 Up to 2 years DoR will be determined according to RECIST v1.1.
Time to Progression (TTP) according to RECIST v1.1 Up to 2 years TTP according to RECIST v1.1.
Nature, frequency, and severity of adverse events (AEs) per NCI CTCAE version 5.0 or higher Up to 2 years 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).
Incidence of SRF388 Antidrug Antibodies (ADAs) Up to 2 years Percentage of patients who develop ADAs to SRF388.
Maximum observed serum concentration (Cmax) of SRF388 Up to 2 years Serum samples will be collected and analyzed to assess the Cmax of SRF388.
PFS according to HCC modified RECIST (mRECIST) Up to 2 years PFS according to HCC mRECIST.
Duration of Response (DoR) according to HCC mRECIST Up to 2 years DoR will be determined according to HCC mRECIST.
Disease Control Rate (DCR) Up to 2 years DCR will measure the proportion of patients who experience best overall response of complete response (CR), partial response (PR), or stable disease (SD).
TTP according to mRECIST Up to 2 years TTP according to HCC mRECIST.
Progression Free Survival (PFS) according to RECIST v1.1 Up to 2 years Progression Free Survival (PFS) according to RECIST v1.1 (Lead-In Phase).
Objective Response Rate (ORR) according to RECIST v1.1 Up to 2 years ORR according to RECIST v1.1.
ORR according to HCC mRECIST Up to 2 years ORR according to HCC mRECIST.
Overall Survival (OS) Up to 2 years OS, defined as time from study drug initiation (Lead-In) or randomization to death from any cause.
Time to Response according to RECIST v1.1 Up to 2 years Time to response will be evaluated according to RECIST v1.1
Time to Response according to HCC mRECIST Up to 2 years Time to response will be evaluated according to HCC mRECIST
Serum concentrations of atezolizumab Up to 2 years Serum samples of atezolizumab will be collected to assess maintenance concentrations of atezolizumab
Incidence of atezolizumab ADAs Up to 2 years Percentage of patients who develop ADAs to atezolizumab.
Area under the serum concentration-time curve from time zero to the last quantifiable time point (AUC0-last) Up to 2 years Serum samples will be collected and analyzed to assess AUC0-last of SRF388.
Time of maximum observed serum concentration (tmax) of SRF388 Up to 2 years Serum samples will be collected and analyzed to assess the (tmax) of SRF388.
Terminal elimination half-life (t1/2) Up to 2 years Serum samples will be collected and analyzed to assess the t1/2 of SRF388.
Trial Locations
- Locations (33)
University of Miami, Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University of Oklahoma Health Sciences Center - Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute - Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Seoul National University Bundang Hospital
🇰🇷Seongnamsi Bundang, Gyeonggi-Do, Korea, Republic of
The Catholic University of Korea - St. Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-Do, Korea, Republic of
CHA University - Bundang CHA General Hospital (CHA Bundang Medical Center)
🇰🇷Gyeonggi-do, Korea, Republic of
Daegu Catholic University Medical Center (DCUMC)
🇰🇷Daegu, Korea, Republic of
City of Hope
🇺🇸Duarte, California, United States
University of Southern California - Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
University of Arizona Cancer Center - North Campus
🇺🇸Tucson, Arizona, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Louisville VA Medical Center - Robley Rex VA Medical Center
🇺🇸Louisville, Kentucky, United States
Veterans Affairs Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center
🇺🇸New York, New York, United States
NYU Langone Medical Center - Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI))
🇺🇸New York, New York, United States
Royal Melbourne Hospital
🇦🇺Melbourne, Australia
Ajou University Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Chonnam National University (CNU) - Chonnam National University Hwasun Hospital (CNUHH)
🇰🇷Jeollanam-do, Korea, Republic of
E-Da Cancer Hospital
🇨🇳Kao-Hsiung, Taiwan
Kaohsiung Medical University - Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳Taipei City, Taiwan
The Alfred Hospital
🇦🇺Melbourne, Australia
University of Michigan Health System (UMHS)
🇺🇸Ann Arbor, Michigan, United States
Pusan National University Yangsan Hospital
🇰🇷Yangsan-si, Gyeongsangnam-do, Korea, Republic of
Buddhist Tzu Chi General Hospital - Hualien Tzu Chi Medical Center
🇨🇳Hualien City, Taiwan
Korea University Medical Center - Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital - Cancer Hospital
🇰🇷Seoul, Korea, Republic of
University of Ulsan College of Medicine - Asan Medical Center (AMC)
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital (SNUH) - SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
China Medical University Hospital
🇨🇳Taichung, Taiwan