Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
- Conditions
- Clear Cell Renal Cell Carcinoma
- Interventions
- Registration Number
- NCT04300140
- Lead Sponsor
- Aravive, Inc.
- Brief Summary
This is a Phase 1b/2 study of AVB-S6-500 designed to evaluate the safety and efficacy of AVB-S6-500 in combination with cabozantinib, AVB-S6-500 in combination with cabozantinib and nivolumab and AVB-S6-500 monotherapy in subjects with advanced or metastatic clear cell renal cell carcinoma (ccRCC). The phase 1b portion of the study is open label and patients with advanced ccRCC who had progressed on or after at least one prior line of treatment will receive AVB-S6-500 + cabozantinib. Two dose levels will be evaluated. The Phase 2 portion of the study is open-label 3-part study to evaluate efficacy and tolerability of AVB-S6-500 + cabozantinib, AVB-S6-500 + cabozantinib + nivolumab, and AVB-S6-500 alone.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 72
- Age 18 years or older
- Histologically confirmed advanced or metastatic clear cell Renal Cell Carcinoma confirmed by imaging. Phase 1b and Phase 2 Part A: has progressed on/after at least one front-line of treatment; Phase 2 Part B: No prior systemic treatment; Phase 2 Part C: not amenable to curative intent therapy.
- Must have radiologic imaging with a computed tomography (CT) scan or magnetic resonance imaging (MRI) within 28 days of enrollment
- Must have at least one measurable lesion according to RECIST 1.1
- ECOG performance status of 0-1
- Adequate bone marrow, liver and kidney function
- Life expectancy of >12 weeks
- At least 28 days between termination of prior major surgery or anticancer therapy or 14 days from last radiation therapy and administration of AVB-S6-500
- Received prior treatment with cabozantinib (Phase1b and Phase 2 Part A)
- Received prior treatment with nivolumab (Phase 2 Part B)
- Concurrent anti-cancer therapy or any other interventional treatment or other interventional research trial
- History of prior malignancy within the past 3 years except adequately treated basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast
- Symptomatic CNS metastasis or metastases
- Active GI disease that would impact absorption of cabozantinib
- Nephrotic range proteinuria at screening
- Evidence of pleural effusion, ascites etc that requires therapeutic intervention within 28 days prior to AVB-S6-500 administration
- Phase 2 Part A and Part B: Has had a major bleed in the last 3 months, uncontrolled hypertension despite treatment with antihypertensives or is not appropriate for treatment with cabozantinib in the Investigator's opinion
- Serious active infection requiring IV antibiotics and/or hospitalization at study entry
- Phase 2 Part B: Has active, known or suspected autoimmune disease, defined as requiring systemic treatment
- Active COVID-19, HIV, Hepatitis B or Hepatitis C virus.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 1b: Batiraxcept + cabozantinib Batiraxcept Two dose levels of batiraxcept administered Q2W (once every two weeks) in combination with QD (once a day) cabozantinib will be evaluated. Phase 1b: Batiraxcept + cabozantinib Cabozantinib (Cabo) Two dose levels of batiraxcept administered Q2W (once every two weeks) in combination with QD (once a day) cabozantinib will be evaluated. Phase 2 Part A: batiraxcept + cabozantinib Batiraxcept One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated. Phase 2 Part A: batiraxcept + cabozantinib Cabozantinib (Cabo) One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated. Phase 2 Part B: batiraxcept + cabozantinib + nivolumab Batiraxcept One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab. Phase 2 Part B: batiraxcept + cabozantinib + nivolumab Cabozantinib (Cabo) One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab. Phase 2 Part B: batiraxcept + cabozantinib + nivolumab Nivolumab One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab. Phase 2 Part C: batiraxcept alone Batiraxcept One dose level of batiraxcept administered Q2W will be evaluated.
- Primary Outcome Measures
Name Time Method Identify the recommended Phase 2 dose of AVB-S6-500 in combination with cabozantinib 10 months Measured by dose limiting toxicities experienced in Phase 1b
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (ORR) 30 months Measured by objective response rate (ORR) in patients receiving AVB-S6-500 + cabozantinib in Phase 1b and Phase 2 Part A. ORR is proportion of subjects who have a partial or complete confirmed response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (ORR) 30 months Measured by objective response rate (ORR) in patients receiving AVB-S6-500 + cabozantinib + nivolumab in Phase 2 Part B. ORR is proportion of subjects who have a partial or complete confirmed response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Anti-tumor activity of AVB-S6-500 alone (DOR) 30 months Measured by duration of response (DOR) in patients receiving AVB-S6-500 in Phase 2 Part C. DOR is measured from the date of partial or complete response to therapy until the cancer progresses.
Anti-tumor activity of AVB-S6-500 alone (CBR) 30 months Measured by clinical benefit rate (CBR) in patients receiving AVB-S6-500 in Phase 2 Part C. CBR is the proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
Anti-tumor activity of AVB-S6-500 alone (PFS) 30 months Measured by progression-free survival (PFS) in patients receiving AVB-S6-500 in Phase 2 Part C. PFS is the time from treatment until radiological disease progression or death.
Incidence of adverse events in Phase 1b as graded by NCI-CTCAE version 5.0 10 months Safety and tolerability of AVB-S6-500 in combination with cabozantinib.
Anti-tumor activity of AVB-S6-500 alone (ORR) 30 months Measured by objective response rate (ORR) in patients receiving AVB-S6-500 in Phase 2 Part C. ORR is proportion of subjects who have a partial or complete confirmed response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Anti-tumor activity of AVB-S6-500 alone (OS) 60 months Measured by overall survival (OS) in patients receiving AVB-S6-500 in Phase 2 Part C. OS is the time from the start of the treatment until death.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics: Tmax 30 months Time of maximum observed AVB-S6-500 concentration.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (CBR) 30 months Measured by clinical benefit rate (CBR) in patients receiving AVB-S6-500, cabozantinib and nivolumab in Phase 2 Part B. CBR is the proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (OS) 60 months Measured by overall survival (OS) in patients receiving AVB-S6-500 in Phase 1b and Phase 2 Part A. OS is the time from the start of the treatment until death.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (DOR) 30 months Measured by duration of response (DOR) in patients receiving AVB-S6-500, cabozantinib and nivolumab in Phase 2 Part B. DOR is measured from the date of partial or complete response to therapy until the cancer progresses.
Incidence of adverse events in Phase 2 Part C as graded by NCI-CTCAE version 5.0 30 months Safety and tolerability of AVB-S6-500 alone
Incidence of adverse events in Phase 2 Part B as graded by NCI-CTCAE version 5.0 30 months Safety and tolerability of AVB-S6-500 in combination with cabozantinib and nivolumab
Pharmacokinetics: Cmax 30 months Maximum observed AVB-S6-500 concentration.
Pharmacokinetics: AUC 30 months Area under the AVB-S6-500 concentration-time curve.
Pharmacodynamic marker assessment 30 months Change from the baseline in GAS6 serum levels.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (CBR) 30 months Measured by clinical benefit rate (CBR) in patients receiving AVB-S6-500 + cabozantinib in Phase 1b and Phase 2 Part A. CBR is the proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
Pharmacokinetics: t1/2 30 months Apparent terminal half-life of AVB-S6-500.
Anti-drug antibody (ADA) titers 30 months Change from baseline in ADA titer.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (DOR) 30 months Measured by duration of response (DOR) in patients receiving AVB-S6-500 in Phase 1b and Phase 2 Part A. DOR is measured from the date of partial or complete response to therapy until the cancer progresses.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (PFS) 30 months Measured by progression-free survival (PFS) in patients receiving AVB-S6-500, cabozantinib and nivolumab in Phase 2 Part B. PFS is the time from treatment until radiological disease progression or death.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (PFS) 30 months Measured by progression-free survival (PFS) in patients receiving AVB-S6-500 in Phase 1b and Phase 2 Part A, PFS is the time from treatment until radiological disease progression or death.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (OS) 60 months Measured by overall survival (OS) in patients receiving AVB-S6-500, cabozantinib and nivolumab in Phase 2 Part B. OS is the time from the start of the treatment until death.
Trial Locations
- Locations (17)
University of Pennsylvania Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
University of Maryland Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Care of Nevada
🇺🇸Las Vegas, Nevada, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
OU Health Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Hollings Cancer Center (HCC)
🇺🇸Charleston, South Carolina, United States
UT MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Vanderbilt-Ingram Cancer Center (VICC)
🇺🇸Nashville, Tennessee, United States