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

Phase 2TerminatedNCT04300140

Aravive, Inc.72 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Clear Cell Renal Cell Carcinoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (17)

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Comprehensive Cancer Care of Nevada

Las Vegas, Nevada, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

...and 7 more locations

Outcomes

Primary Outcomes

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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 60 months

Secondary Outcomes

Pharmacokinetics: AUC

Area under the AVB-S6-500 concentration-time curve.

Time frame: 30 months

Pharmacokinetics: Cmax

Maximum observed AVB-S6-500 concentration.

Time frame: 30 months

Pharmacokinetics: Tmax

Time of maximum observed AVB-S6-500 concentration.

Time frame: 30 months

Pharmacokinetics: t1/2

Apparent terminal half-life of AVB-S6-500.

Time frame: 30 months

Pharmacodynamic marker assessment

Change from the baseline in GAS6 serum levels.

Time frame: 30 months

Anti-drug antibody (ADA) titers

Change from baseline in ADA titer.

Time frame: 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.

Time frame: 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.

Time frame: 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.

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 60 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

Time frame: 30 months