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

Clear Cell Renal Cell Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04300140
• Other study ID #: AVB500-RCC-003
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 26, 2021
• Est. completion date: August 14, 2023

Study information

• Verified date: October 2023
• Source: Aravive, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: August 14, 2023
• Est. primary completion date: August 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Clear Cell Renal Cell Carcinoma

Intervention

Drug:
• Batiraxcept
Batiraxcept is experimental drug
• Cabozantinib (Cabo)
Cabozantinib is standard of care as monotherapy and in combination with nivolumab in ccRCC
• Nivolumab
Nivolumab is standard of care in the first line treatment of ccRCC

Locations

Country	Name	City	State
United States	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Hollings Cancer Center (HCC)	Charleston	South Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Care of Nevada	Las Vegas	Nevada
United States	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt-Ingram Cancer Center (VICC)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Allegheny Health Network	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Aravive, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Pharmacokinetics: AUC	Area under the AVB-S6-500 concentration-time curve.	30 months
Secondary	Pharmacokinetics: Cmax	Maximum observed AVB-S6-500 concentration.	30 months
Secondary	Pharmacokinetics: Tmax	Time of maximum observed AVB-S6-500 concentration.	30 months
Secondary	Pharmacokinetics: t1/2	Apparent terminal half-life of AVB-S6-500.	30 months
Secondary	Pharmacodynamic marker assessment	Change from the baseline in GAS6 serum levels.	30 months
Secondary	Anti-drug antibody (ADA) titers	Change from baseline in ADA titer.	30 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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