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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.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Clear Cell Renal Cell Carcinoma Drug: Batiraxcept Drug: Cabozantinib (Cabo) Drug: Nivolumab Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 26, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : March 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 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®
Experimental: Phase 2 Part A: batiraxcept + cabozantinib
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated.
 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®
Experimental: Phase 2 Part B: batiraxcept + cabozantinib + nivolumab
One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab.
 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®
Experimental: Phase 2 Part C: batiraxcept alone
One dose level of batiraxcept administered Q2W will be evaluated.
 Drug: Batiraxcept
Batiraxcept is experimental drug
Other Name: AVB-S6-500


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.


Secondary Outcome Measures :
  1. Pharmacokinetics: AUC [ Time Frame: 30 months ]
    Area under the AVB-S6-500 concentration-time curve.

  2. Pharmacokinetics: Cmax [ Time Frame: 30 months ]
    Maximum observed AVB-S6-500 concentration.

  3. Pharmacokinetics: Tmax [ Time Frame: 30 months ]
    Time of maximum observed AVB-S6-500 concentration.

  4. Pharmacokinetics: t1/2 [ Time Frame: 30 months ]
    Apparent terminal half-life of AVB-S6-500.

  5. Pharmacodynamic marker assessment [ Time Frame: 30 months ]
    Change from the baseline in GAS6 serum levels.

  6. Anti-drug antibody (ADA) titers [ Time Frame: 30 months ]
    Change from baseline in ADA titer.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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


Eligibility Criteria
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Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04300140


Locations
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Sponsors and Collaborators
Aravive, Inc.
More Information
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Responsible Party: Aravive, Inc.
ClinicalTrials.gov Identifier: NCT04300140    
Other Study ID Numbers: AVB500-RCC-003
First Posted: March 9, 2020    Key Record Dates
Last Update Posted: January 18, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aravive, Inc.:
Clear cell renal cell carcinoma
Renal cell carcinoma
Recurrent renal cell carcinoma
Kidney cancer
 Kidney Neoplasms
Kidney Diseases
Urologic Neoplasms
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Female Urogenital Diseases
 Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Kidney Diseases
Urologic Diseases
Male Urogenital Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action