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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
SRF388 will be administered by intravenous injection (IV)
Azezolizumab will be administered by IV
Bevacizumab will be administered by IV
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).
Time frame: 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).
Time frame: Up to 2 years
Progression Free Survival (PFS) according to RECIST v1.1
Progression Free Survival (PFS) according to RECIST v1.1 (Lead-In Phase).
Time frame: Up to 2 years
PFS according to HCC modified RECIST (mRECIST)
PFS according to HCC mRECIST.
Time frame: Up to 2 years
Objective Response Rate (ORR) according to RECIST v1.1
ORR according to RECIST v1.1.
Time frame: Up to 2 years
ORR according to HCC mRECIST
ORR according to HCC mRECIST.
Time frame: Up to 2 years
Duration of Response (DoR) according to RECIST 1.1
DoR will be determined according to RECIST v1.1.
Time frame: Up to 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Placebo will be administered by IV
University of Arizona Cancer Center - North Campus
Tucson, Arizona, United States
City of Hope
Duarte, California, United States
University of Southern California - Norris Comprehensive Cancer Center
Los Angeles, California, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States
University of Miami, Sylvester Comprehensive Cancer Center
Miami, 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
University of Michigan Health System (UMHS)
Ann Arbor, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Veterans Affairs New York Harbor Healthcare System - Manhattan VA Medical Center
New York, New York, United States
...and 27 more locations
Duration of Response (DoR) according to HCC mRECIST
DoR will be determined according to HCC mRECIST.
Time frame: 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).
Time frame: Up to 2 years
Time to Progression (TTP) according to RECIST v1.1
TTP according to RECIST v1.1.
Time frame: Up to 2 years
TTP according to mRECIST
TTP according to HCC mRECIST.
Time frame: Up to 2 years
Overall Survival (OS)
OS, defined as time from study drug initiation (Lead-In) or randomization to death from any cause.
Time frame: Up to 2 years
Time to Response according to RECIST v1.1
Time to response will be evaluated according to RECIST v1.1
Time frame: Up to 2 years
Time to Response according to HCC mRECIST
Time to response will be evaluated according to HCC mRECIST
Time frame: 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).
Time frame: Up to 2 years
Incidence of SRF388 Antidrug Antibodies (ADAs)
Percentage of patients who develop ADAs to SRF388.
Time frame: Up to 2 years
Incidence of atezolizumab ADAs
Percentage of patients who develop ADAs to atezolizumab.
Time frame: Up to 2 years
Maximum observed serum concentration (Cmax) of SRF388
Serum samples will be collected and analyzed to assess the Cmax of SRF388.
Time frame: 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.
Time frame: 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.
Time frame: Up to 2 years
Terminal elimination half-life (t1/2)
Serum samples will be collected and analyzed to assess the t1/2 of SRF388.
Time frame: Up to 2 years
Serum concentrations of atezolizumab
Serum samples of atezolizumab will be collected to assess maintenance concentrations of atezolizumab
Time frame: Up to 2 years