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Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04300140
Recruitment Status : Active, not recruiting
First Posted : March 9, 2020
Last Update Posted : January 18, 2023
Sponsor:
Information provided by (Responsible Party):
Aravive, Inc.

Tracking Information
First Submitted Date  ICMJE March 5, 2020
First Posted Date  ICMJE March 9, 2020
Last Update Posted Date January 18, 2023
Actual Study Start Date  ICMJE February 26, 2021
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2021)
  • Incidence of adverse events in Phase 1b as graded by NCI-CTCAE version 5.0 [ Time Frame: 10 months ]
    Safety and tolerability of AVB-S6-500 in combination with cabozantinib.
  • Identify the recommended Phase 2 dose of AVB-S6-500 in combination with cabozantinib [ Time Frame: 10 months ]
    Measured by dose limiting toxicities experienced in Phase 1b
  • Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (ORR) [ Time Frame: 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) [ Time Frame: 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 (ORR) [ Time Frame: 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 (DOR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
  • Anti-tumor activity of AVB-S6-500 alone (OS) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 5, 2020)
  • Incidence of Adverse Events (AEs) [ Time Frame: 9 months ]
    Measured by the number of patients with AEs in Phase 1 portion of the study.
  • Anti-tumor activity of AVB-S6-500 in combination with Cabozantinib [ Time Frame: 30 months ]
    Measured by progression free survival (PFS) in patients receiving AVB-S6-500+Cabo versus patients receiving Cabo alone in Phase 2 portion of the study.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2021)
  • Pharmacokinetics: AUC [ Time Frame: 30 months ]
    Area under the AVB-S6-500 concentration-time curve.
  • Pharmacokinetics: Cmax [ Time Frame: 30 months ]
    Maximum observed AVB-S6-500 concentration.
  • Pharmacokinetics: Tmax [ Time Frame: 30 months ]
    Time of maximum observed AVB-S6-500 concentration.
  • Pharmacokinetics: t1/2 [ Time Frame: 30 months ]
    Apparent terminal half-life of AVB-S6-500.
  • Pharmacodynamic marker assessment [ Time Frame: 30 months ]
    Change from the baseline in GAS6 serum levels.
  • Anti-drug antibody (ADA) titers [ Time Frame: 30 months ]
    Change from baseline in ADA titer.
  • Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (CBR) [ Time Frame: 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.
  • Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (DOR) [ Time Frame: 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 (OS) [ Time Frame: 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 (PFS) [ Time Frame: 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 (DOR) [ Time Frame: 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.
  • Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (CBR) [ Time Frame: 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 and nivolumab (PFS) [ Time Frame: 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 and nivolumab (OS) [ Time Frame: 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.
  • Incidence of adverse events in Phase 2 Part C as graded by NCI-CTCAE version 5.0 [ Time Frame: 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 [ Time Frame: 30 months ]
    Safety and tolerability of AVB-S6-500 in combination with cabozantinib and nivolumab
Original Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2020)
  • Pharmacokinetics: AUC [ Time Frame: 30 months ]
    Area under the AVB-S6-500 concentration-time curve.
  • Pharmacokinetics: Cmax [ Time Frame: 30 months ]
    Maximum observed AVB-S6-500 concentration.
  • Pharmacokinetics: Tmax [ Time Frame: 30 months ]
    Time of maximum observed AVB-S6-500 concentration.
  • Pharmacokinetics: t1/2 [ Time Frame: 30 months ]
    Apparent terminal half-life of AVB-S6-500.
  • Pharmacodynamic marker assessment [ Time Frame: 30 months ]
    Change from the baseline in GAS6 serum levels.
  • Anti-drug antibody (ADA) titers [ Time Frame: 30 months ]
    Change from baseline in ADA titer.
  • Objective response rate [ Time Frame: 30 months ]
    Proportion of subjects who have a partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Disease control rate [ Time Frame: 30 months ]
    Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
  • Duration of response (DOR) [ Time Frame: 30 months ]
    Measured from the date of partial or complete response to therapy until the cancer progresses.
  • Overall survival [ Time Frame: 60 months ]
    Time following the treatment until death.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
Official Title  ICMJE A Phase 1b/2 Study Of AVB-S6-500 In Combination With Cabozantinib, AVB-S6-500 In Combination With Cabozantinib and Nivolumab, and AVB-S6-500 Monotherapy in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Clear Cell Renal Cell Carcinoma
Intervention  ICMJE
  • Drug: Batiraxcept
    Batiraxcept is experimental drug
    Other Name: AVB-S6-500
  • Drug: Cabozantinib (Cabo)
    Cabozantinib is standard of care as monotherapy and in combination with nivolumab in ccRCC
    Other Name: Cabometyx®
  • Drug: Nivolumab
    Nivolumab is standard of care in the first line treatment of ccRCC
    Other Name: Opdivo®
Study Arms  ICMJE
  • Experimental: Phase 1b: Batiraxcept + cabozantinib
    Two dose levels of batiraxcept administered Q2W (once every two weeks) in combination with QD (once a day) cabozantinib will be evaluated.
    Interventions:
    • Drug: Batiraxcept
    • Drug: Cabozantinib (Cabo)
  • Experimental: Phase 2 Part A: batiraxcept + cabozantinib
    One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated.
    Interventions:
    • Drug: Batiraxcept
    • Drug: Cabozantinib (Cabo)
  • Experimental: Phase 2 Part B: batiraxcept + cabozantinib + nivolumab
    One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab.
    Interventions:
    • Drug: Batiraxcept
    • Drug: Cabozantinib (Cabo)
    • Drug: Nivolumab
  • Experimental: Phase 2 Part C: batiraxcept alone
    One dose level of batiraxcept administered Q2W will be evaluated.
    Intervention: Drug: Batiraxcept
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 17, 2021)
80
Original Estimated Enrollment  ICMJE
 (submitted: March 5, 2020)
108
Estimated Study Completion Date  ICMJE March 2025
Estimated Primary Completion Date December 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04300140
Other Study ID Numbers  ICMJE AVB500-RCC-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Aravive, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Aravive, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Aravive, Inc.
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP