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

Sponsor

Aravive, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04300140

Collaborator

(none)

Enrollment

Locations

Arms

28.1

Anticipated Duration (Months)

4.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Anticipated 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 :

Feb 26, 2021

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Incidence of adverse events in Phase 1b as graded by NCI-CTCAE version 5.0 [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 [10 months]
Measured by dose limiting toxicities experienced in Phase 1b
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (ORR) [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) [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) [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) [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) [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) [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) [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

Pharmacokinetics: AUC [30 months]
Area under the AVB-S6-500 concentration-time curve.
Pharmacokinetics: Cmax [30 months]
Maximum observed AVB-S6-500 concentration.
Pharmacokinetics: Tmax [30 months]
Time of maximum observed AVB-S6-500 concentration.
Pharmacokinetics: t1/2 [30 months]
Apparent terminal half-life of AVB-S6-500.
Pharmacodynamic marker assessment [30 months]
Change from the baseline in GAS6 serum levels.
Anti-drug antibody (ADA) titers [30 months]
Change from baseline in ADA titer.
Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (CBR) [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) [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) [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) [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) [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) [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) [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) [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 [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 [30 months]
Safety and tolerability of AVB-S6-500 in combination with cabozantinib and nivolumab

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland Greenebaum Comprehensive Cancer Center	Baltimore	Maryland	United States	21201
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
4	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
5	Comprehensive Cancer Care of Nevada	Las Vegas	Nevada	United States	89169
6	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
7	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10024
8	Duke University Medical Center	Durham	North Carolina	United States	27710
9	Cleveland Clinic	Cleveland	Ohio	United States	44195
10	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
11	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
12	Allegheny Health Network	Pittsburgh	Pennsylvania	United States	15212
13	Hollings Cancer Center (HCC)	Charleston	South Carolina	United States	29425
14	Vanderbilt-Ingram Cancer Center (VICC)	Nashville	Tennessee	United States	37232
15	University of Texas Southwestern	Dallas	Texas	United States	75390
16	UT MD Anderson Cancer Center	Houston	Texas	United States	77030
17	Froedtert Hospital and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226