CAB-AXL-ADC Safety and Efficacy Study in Adult and Adolescent Patients with Sarcoma
- Conditions
- MyxofibrosarcomaUndifferentiated Pleomorphic Sarcoma
- Interventions
- Biological: PD-1 inhibitor
- Registration Number
- NCT03425279
- Lead Sponsor
- BioAtla, Inc.
- Brief Summary
The objective of this study is to assess the safety and efficacy of mecbotamab vedotin (BA3011) in solid tumors.
- Detailed Description
This is a multi-center, open-label, Phase 1/2 study designed to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of mecbotamab vedotin (BA3011), a conditionally active biologic (CAB) AXL-targeted antibody drug conjugate (CAB-AXL-ADC) in patients with advanced solid tumors.
Phase 1 of this study will consist of a dose escalation phase (enrollment complete as of Oct 2019) and a dose expansion phase (enrollment complete as of Jan 2024).
Phase 2 will consist of two parts. Part 1 is designed to evaluate mecbotamab vedotin alone and with nivolumab in patients with various types of advanced sarcomas (enrollment complete as of Jan 2024). Part 2 will evaluate the safety and efficacy of mecbotamab vedotin in patients with undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 300
- Patients must have measurable disease.
- Age ≥ 12 years (Phase 2)
- Adequate renal function
- Adequate liver function
- Adequate hematological function
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of at least three months.
- Patients must not have clinically significant cardiac disease.
- Patients must not have known non-controlled CNS metastasis.
- Patients must not have a history of ≥ Grade 3 allergic reactions to mAb therapy as well as known or suspected allergy or intolerance to any agent given during this study.
- Patients must not have had major surgery within 4 weeks before first BA3011 administration.
- Patients must not have had prior therapy with a conjugated or unconjugated auristatin derivative/vinca-binding site targeting payload.
- Patients must not have known human immunodeficiency virus (HIV) infection, active hepatitis B and/or hepatitis C.
- Patients must not be women who are pregnant or breast feeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination Therapy CAB-AXL-ADC Phase 2: BA3011 in combination with PD-1 inhibitor. Combination Therapy PD-1 inhibitor Phase 2: BA3011 in combination with PD-1 inhibitor. BA3011 CAB-AXL-ADC Phase 1: All patients will receive BA3011, CAB-AXL-ADC. Phase 2: All patients will receive either BA3011 alone or in combination with PD-1 inhibitor.
- Primary Outcome Measures
Name Time Method Phase 1 and 2: Safety Profile Up to 24 months Frequency and severity of AEs and/or SAEs, and changes from baseline in laboratory parameters and vital signs
Phase 2: Confirmed overall response rate (ORR) per RECIST v1.1 Up to 24 months Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1
Phase 1: Safety Profile Up to 24 months Assess maximum tolerated dose as defined in the protocol
- Secondary Outcome Measures
Name Time Method Phase 1: Overall response rate (ORR) Up to 24 months Proportion of patients who achieve a confirmed CR or PR
Phase 1: Immunogenicity Up to 24 months The number and percentage of patients who develop detectable anti-drug antibodies (ADAs)
Phase 1 and 2: Time to response (TTR) Up to 24 months Time from the first dose of investigational product until the first documentation of OR
Phase 1 and 2: Overall survival (OS) Up to 24 months Time from the first dose of BA3011 treatment until death due to any cause
Phase 1: Pharmacokinetics Up to 24 months Area under the plasma concentration versus time curve (AUC)
Phase 1 and 2: Best overall response (BOR) Up to 24 months All post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy
Phase 1 and 2: Duration of response (DOR) Up to 24 months Time from the first documented OR until the first documented disease progression or death (due to any cause), whichever occurs first
Phase 1 and 2: Disease control rate (DCR) Up to 24 months Proportion of patients with a best overall response of confirmed CR, confirmed PR, or stable disease (SD) ≥ 12 weeks
Phase 1 and 2: Tumor size Up to 24 months Percent change from baseline in tumor size
Phase 1 and 2: Progression-free survival (PFS) Up to 24 months Time from the first dose of IP until the first documentation of disease progression or death due to any cause, whichever occurs first
Trial Locations
- Locations (40)
The University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Tower Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Precision NextGen Oncology
🇺🇸Los Angeles, California, United States
UCSF Medical Center - Cancer Immunotherapy Clinic (CIC)
🇺🇸San Francisco, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Sarah Cannon Research Institute at Health One
🇺🇸Denver, Colorado, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Children's Research Institute
🇺🇸Washington, D.C., District of Columbia, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Comprehensive Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Columbia University
🇺🇸New York, New York, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
The Christ Hospital
🇺🇸Cincinnati, Ohio, United States
University Hospitals Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Abramson Cancer Center at Pennsylvania Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Froedtert Hospital and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Utah - Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan