Hepatocellular Carcinoma
Conditions
Keywords
Phase 2, SRF388, IL-27, safety, efficacy, immunotherapy, cancer, immuno-oncology, liver cancer, hepatocellular carcinoma, atezolizumab, Tecentriq, bevacizumab, Avastin
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).
Interventions
DRUGSRF388
SRF388 will be administered by intravenous injection (IV)
DRUGAtezolizumab
Azezolizumab will be administered by IV
DRUGBevacizumab
Bevacizumab will be administered by IV
DRUGPlacebo
Placebo will be administered by IV
Sponsors
Coherus Oncology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| PFS according to HCC modified RECIST (mRECIST) | Up to 2 years | PFS according to HCC mRECIST. |
| 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. |
| Duration of Response (DoR) according to RECIST 1.1 | Up to 2 years | DoR will be determined according to RECIST v1.1. |
| 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). |
| Time to Progression (TTP) according to RECIST v1.1 | Up to 2 years | TTP according to RECIST v1.1. |
| TTP according to mRECIST | Up to 2 years | TTP 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 |
| 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. |
| Incidence of atezolizumab ADAs | Up to 2 years | Percentage of patients who develop ADAs to atezolizumab. |
| Maximum observed serum concentration (Cmax) of SRF388 | Up to 2 years | Serum samples will be collected and analyzed to assess the Cmax 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. |
| 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. |
| Terminal elimination half-life (t1/2) | Up to 2 years | Serum samples will be collected and analyzed to assess the t1/2 of SRF388. |
| Serum concentrations of atezolizumab | Up to 2 years | Serum samples of atezolizumab will be collected to assess maintenance concentrations of atezolizumab |
Countries
Australia, South Korea, Taiwan, United States
Contacts
STUDY_CHAIRKoho Iizuka, MD
Coherus Oncology, Inc.
Outcome results
None listed