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

• ClinicalTrials.gov Identifier: NCT04300140
• Recruitment Status: Active, not recruiting
• First Posted: March 9, 2020
• Last Update Posted: January 18, 2023
• Sponsor: Aravive, Inc.
• Information provided by (Responsible Party): Aravive, Inc.

Tracking Information

• First Submitted Date: March 5, 2020
• First Posted Date: March 9, 2020
• Last Update Posted Date: January 18, 2023
• Actual Study Start Date: February 26, 2021
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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: Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Clear Cell Renal Cell Carcinoma

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 17, 2021): 80
• Original Estimated Enrollment (submitted: March 5, 2020): 108
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: December 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04300140
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Aravive, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Aravive, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Aravive, Inc.
• Verification Date: January 2023