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

NCT04300140 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AVB500-RCC-003
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 17

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.

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

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (16)

• Pharmacokinetics: AUC

  30 months

• Pharmacokinetics: Cmax

  30 months

• Pharmacokinetics: Tmax

  30 months

• Pharmacokinetics: t1/2

  30 months

• Pharmacodynamic marker assessment

  30 months

Study Arms (4)

Phase 1b: Batiraxcept + cabozantinib

EXPERIMENTAL

Two dose levels of batiraxcept administered Q2W (once every two weeks) in combination with QD (once a day) cabozantinib will be evaluated.

Drug: Batiraxcept; Drug: Cabozantinib (Cabo)

Phase 2 Part A: batiraxcept + cabozantinib

EXPERIMENTAL

One dose level of batiraxcept administered Q2W in combination with QD cabozantinib will be evaluated.

Drug: Batiraxcept; Drug: Cabozantinib (Cabo)

Phase 2 Part B: batiraxcept + cabozantinib + nivolumab

EXPERIMENTAL

One dose level of batiraxcept administered Q2W in combination with QD cabozantinib and nivolumab.

Drug: Batiraxcept; Drug: Cabozantinib (Cabo); Drug: Nivolumab

Phase 2 Part C: batiraxcept alone

EXPERIMENTAL

One dose level of batiraxcept administered Q2W will be evaluated.

Drug: Batiraxcept

Interventions

Batiraxcept DRUG

Batiraxcept is experimental drug

Also known as: AVB-S6-500

Phase 1b: Batiraxcept + cabozantinib; Phase 2 Part A: batiraxcept + cabozantinib; Phase 2 Part B: batiraxcept + cabozantinib + nivolumab; Phase 2 Part C: batiraxcept alone

Cabozantinib (Cabo) DRUG

Cabozantinib is standard of care as monotherapy and in combination with nivolumab in ccRCC

Also known as: Cabometyx®

Phase 1b: Batiraxcept + cabozantinib; Phase 2 Part A: batiraxcept + cabozantinib; Phase 2 Part B: batiraxcept + cabozantinib + nivolumab

Nivolumab DRUG

Nivolumab is standard of care in the first line treatment of ccRCC

Also known as: Opdivo®

Phase 2 Part B: batiraxcept + cabozantinib + nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aravive, Inc.: lead

Study Sites (17)

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Comprehensive Cancer Care of Nevada

Las Vegas, Nevada, 89169, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10024, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

Hollings Cancer Center (HCC)

Charleston, South Carolina, 29425, United States

Location

Vanderbilt-Ingram Cancer Center (VICC)

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Beckermann KE, Shah NJ, Campbell MT, Haas NB, Nelson A, Ornstein MC, Mao S, Keshava-Prasad HS, Hammers H, Gao X, Gourdin T, George S, Hoimes CJ, Hussain A, Jonasch E, Rini BI, Voss MH. Phase 1b/2 study of batiraxcept alone and in combination with cabozantinib with or without nivolumab for advanced clear cell renal cell carcinoma. Oncologist. 2025 Jun 4;30(6):oyaf138. doi: 10.1093/oncolo/oyaf138.

  PMID: 40549043 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Kidney Diseases; Urologic Neoplasms

Interventions

cabozantinib; VMBP protocol; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2020
• First Posted: March 9, 2020
• Study Start: February 26, 2021
• Primary Completion: August 14, 2023
• Study Completion: August 14, 2023
• Last Updated: October 30, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)