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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: Batiraxcept; Drug: Cabozantinib (Cabo); Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Care of Nevada
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10024
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Health Network
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center (HCC)
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center (VICC)
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • Houston, Texas, United States, 77030
      • UT MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: AVB-S6-500; Drug: Cabozantinib (Cabo); Cabozantinib is standard of care as monotherapy and in combination with nivolumab in ccRCC; Other Names: 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 Names: AVB-S6-500; Drug: Cabozantinib (Cabo); Cabozantinib is standard of care as monotherapy and in combination with nivolumab in ccRCC; Other Names: 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 Names: AVB-S6-500; Drug: Cabozantinib (Cabo); Cabozantinib is standard of care as monotherapy and in combination with nivolumab in ccRCC; Other Names: Cabometyx®; Drug: Nivolumab; Nivolumab is standard of care in the first line treatment of ccRCC; Other Names: 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 Names: AVB-S6-500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events in Phase 1b as graded by NCI-CTCAE version 5.0	Safety and tolerability of AVB-S6-500 in combination with cabozantinib.	10 months
Identify the recommended Phase 2 dose of AVB-S6-500 in combination with cabozantinib	Measured by dose limiting toxicities experienced in Phase 1b	10 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (ORR)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (ORR)	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.	30 months
Anti-tumor activity of AVB-S6-500 alone (ORR)	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.	30 months
Anti-tumor activity of AVB-S6-500 alone (DOR)	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.	30 months
Anti-tumor activity of AVB-S6-500 alone (CBR)	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.	30 months
Anti-tumor activity of AVB-S6-500 alone (PFS)	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.	30 months
Anti-tumor activity of AVB-S6-500 alone (OS)	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.	60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: AUC	Area under the AVB-S6-500 concentration-time curve.	30 months
Pharmacokinetics: Cmax	Maximum observed AVB-S6-500 concentration.	30 months
Pharmacokinetics: Tmax	Time of maximum observed AVB-S6-500 concentration.	30 months
Pharmacokinetics: t1/2	Apparent terminal half-life of AVB-S6-500.	30 months
Pharmacodynamic marker assessment	Change from the baseline in GAS6 serum levels.	30 months
Anti-drug antibody (ADA) titers	Change from baseline in ADA titer.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (CBR)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (DOR)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (OS)	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.	60 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (PFS)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (DOR)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (CBR)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (PFS)	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.	30 months
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (OS)	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.	60 months
Incidence of adverse events in Phase 2 Part C as graded by NCI-CTCAE version 5.0	Safety and tolerability of AVB-S6-500 alone	30 months
Incidence of adverse events in Phase 2 Part B as graded by NCI-CTCAE version 5.0	Safety and tolerability of AVB-S6-500 in combination with cabozantinib and nivolumab	30 months

Collaborators and Investigators

• Sponsor: Aravive, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2021
• Primary Completion (Actual): August 14, 2023
• Study Completion (Actual): August 14, 2023

Study Registration Dates

• First Submitted: March 5, 2020
• First Submitted That Met QC Criteria: March 5, 2020
• First Posted (Actual): March 9, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Kidney cancer; Kidney Diseases; Kidney Neoplasms; Renal cell carcinoma; Urologic Neoplasms; Clear cell renal cell carcinoma; Recurrent renal cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: AVB500-RCC-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No