CAB-AXL-ADC Safety and Efficacy Study in Adult and Adolescent Patients With Sarcoma

A Phase 1/2 Dose Escalation and Dose Expansion Study of Mecbotamab Vedotin (BA3011) Alone and in Combination With Nivolumab in Adult and Adolescent Patients 12 Years and Older With Advanced Solid Tumors

The objective of this study is to assess the safety and efficacy of mecbotamab vedotin (BA3011) in solid tumors.

Study Overview

• Status: Completed
• Conditions: Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma
• Intervention / Treatment: Biological: CAB-AXL-ADC; Biological: PD-1 inhibitor

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).

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• Taiwan
  • Tainan City, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan District, Taiwan
    • Chang Gung Memorial Hospital
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • The University of Arizona Cancer Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90048
      • Tower Hematology Oncology Medical Group
    • Los Angeles, California, United States, 90212
      • Precision NextGen Oncology
    • San Francisco, California, United States, 94158
      • UCSF Medical Center - Cancer Immunotherapy Clinic (CIC)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University Of Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at Health ONE
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's Research Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine - Siteman Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Center of Nevada
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Christ Hospital
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Seidman Cancer Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19106
      • Abramson Cancer Center at Pennsylvania Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah - Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Therapy; Phase 2: BA3011 in combination with PD-1 inhibitor.	Biological: CAB-AXL-ADC; Conditionally active biologic anti-AXL antibody drug conjugate; Biological: PD-1 inhibitor; PD-1 inhibitor
Experimental: BA3011; 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.	Biological: CAB-AXL-ADC; Conditionally active biologic anti-AXL antibody drug conjugate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Safety Profile	Assess dose limiting toxicity as defined in the protocol	Up to 24 months
Phase 1: Safety Profile	Assess maximum tolerated dose as defined in the protocol	Up to 24 months
Phase 2: Confirmed overall response rate (ORR) per RECIST v1.1	Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1	Up to 24 months
Phase 1 and 2: Safety Profile	Frequency and severity of AEs and/or SAEs, and changes from baseline in laboratory parameters and vital signs	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Pharmacokinetics	Plasma concentrations of ADC, total antibody and MMAE	Up to 24 months
Phase 1: Pharmacokinetics	Peak Plasma Concentration (Cmax)	Up to 24 months
Phase 1: Pharmacokinetics	Area under the plasma concentration versus time curve (AUC)	Up to 24 months
Phase 1: Overall response rate (ORR)	Proportion of patients who achieve a confirmed CR or PR	Up to 24 months
Phase 1: Immunogenicity	The number and percentage of patients who develop detectable anti-drug antibodies (ADAs)	Up to 24 months
Phase 1 and 2: Duration of response (DOR)	Time from the first documented OR until the first documented disease progression or death (due to any cause), whichever occurs first	Up to 24 months
Phase 1 and 2: Progression-free survival (PFS)	Time from the first dose of IP until the first documentation of disease progression or death due to any cause, whichever occurs first	Up to 24 months
Phase 1 and 2: Disease control rate (DCR)	Proportion of patients with a best overall response of confirmed CR, confirmed PR, or stable disease (SD) ≥ 12 weeks	Up to 24 months
Phase 1 and 2: Time to response (TTR)	Time from the first dose of investigational product until the first documentation of OR	Up to 24 months
Phase 1 and 2: Overall survival (OS)	Time from the first dose of BA3011 treatment until death due to any cause	Up to 24 months
Phase 1 and 2: Tumor size	Percent change from baseline in tumor size	Up to 24 months
Phase 1 and 2: Best overall response (BOR)	All post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy	Up to 24 months

Collaborators and Investigators

• Sponsor: BioAtla, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2018
• Primary Completion (Actual): January 8, 2025
• Study Completion (Actual): January 8, 2025

Study Registration Dates

• First Submitted: January 22, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 7, 2018

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: cancer; late stage; stage 3; stage 4; undifferentiated pleomorphic sarcoma; myxofibrosarcoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Fibrosarcoma; Neoplasms, Fibrous Tissue; Histiocytoma; Neoplasms; Histiocytoma, Malignant Fibrous; Dermatofibrosarcoma; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors
• Other Study ID Numbers: BA3011-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No