Clinical trial NCT04300140: Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Clear Cell Renal Cell Carcinoma
Keywords: Clear cell renal cell carcinoma
Renal cell carcinoma
Recurrent renal cell carcinoma
Kidney cancer
Kidney Neoplasms
Kidney Diseases
Urologic Neoplasms
Lead sponsor: Aravive, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-09
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Incidence of adverse events in Phase 1b as graded by NCI-CTCAE version 5.0
timeFrame: 10 months
measure: Identify the recommended Phase 2 dose of AVB-S6-500 in combination with cabozantinib
timeFrame: 10 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (ORR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (ORR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 alone (ORR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 alone (DOR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 alone (CBR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 alone (PFS)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 alone (OS)
timeFrame: 60 months
Secondary outcomes:
measure: Pharmacokinetics: AUC
timeFrame: 30 months
measure: Pharmacokinetics: Cmax
timeFrame: 30 months
measure: Pharmacokinetics: Tmax
timeFrame: 30 months
measure: Pharmacokinetics: t1/2
timeFrame: 30 months
measure: Pharmacodynamic marker assessment
timeFrame: 30 months
measure: Anti-drug antibody (ADA) titers
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (CBR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (DOR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (OS)
timeFrame: 60 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib (PFS)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (DOR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (CBR)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (PFS)
timeFrame: 30 months
measure: Anti-tumor activity of AVB-S6-500 in combination with cabozantinib and nivolumab (OS)
timeFrame: 60 months
measure: Incidence of adverse events in Phase 2 Part C as graded by NCI-CTCAE version 5.0
timeFrame: 30 months
measure: Incidence of adverse events in Phase 2 Part B as graded by NCI-CTCAE version 5.0
timeFrame: 30 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Care of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center (HCC)
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center (VICC)
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
Study officials:
References: