A Dose Escalation Study of AV-380 in Cancer Patients With Cachexia

A Phase 1B Dose Escalation Study of AV-380 in Combination With Standard of Care Chemotherapy in Metastatic Cancer Patients With Cachexia and Elevated GDF-15 Levels

This open label ascending dose study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AV-380 in cancer patients with Cachexia. AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.

Study Overview

• Status: Recruiting
• Conditions: Cachexia
• Intervention / Treatment: Biological: AV-380

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AVEO Clinical Trials Office; Phone Number: (857)400-0101; Email: clinical@aveooncology.com

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Recruiting
      • Beverly Hills Cancer Center
    • Lakewood, California, United States, 90712
      • Recruiting
      • Cancer and Blood Specialty Clinic
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Recruiting
      • Hartford Hospital
  • Florida
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Advent Health Orlando Hospital
      • Contact: Corina Mattix; Phone Number: 407-303-1327; Email: Corina.Mattix@AdventHealth.com
      • Contact: Iman Boudlal; Email: iman.boudlal@adventhealth.com
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialists
  • New Jersey
    • East Brunswick, New Jersey, United States, 08816
      • Recruiting
      • Astera Cancer Care
  • New York
    • Shirley, New York, United States, 11967
      • Recruiting
      • New York Cancer and Blood Specialists
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • MUSC Hollings Cancer Center
      • Contact: Bria Sanders; Email: sandebri@musc.edu
      • Contact: Carly Fecio; Phone Number: (843)792-3479; Email: fecio@musc.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Henry-Joyce Cancer Clinic
  • Texas
    • Kingwood, Texas, United States, 77339
      • Recruiting
      • Community Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient must be ≥ 18 years of age at the time of signing the informed consent.
2. Patients with histologically confirmed solid tumor cancer who are actively receiving SoC therapy for this cancer.

3. Patients with cachexia as defined by Fearon criteria:

   1. Weight loss > 5% over past 6 months (in absence of simple starvation), or
   2. BMI < 20 kg/m2 and any degree of weight loss > 2%, or
   3. Sarcopenia and any degree of weight loss > 2%
4. Patients with life expectancy ≥ 3 months

Exclusion Criteria:

1. History of allergic or anaphylactic reaction to any monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibody
2. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 2 weeks before first dose of study treatment.
3. Myocardial infarction or heart failure of New York Heart Association Grade 3-4 within 3 months prior to start of protocol therapy
4. Uncontrolled pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
5. Cachexia is caused by other reasons (e.g., severe chronic obstructive pulmonary disease, heart failure, or HIV/AIDS), or the patient has uncontrolled reversible causes of reduced oral food intake, including, but not limited to, oral mucositis, nausea/vomiting, diarrhea, and/or obstruction, impairing the patient's ability to eat as determined by the Investigator.
6. Patients receiving tube feedings or parenteral nutrition at the time of Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohorts; Experimental: Dose escalation cohorts of AV-380 administered by IV infusion	Biological: AV-380; AV-380 is an immunoglobulin (Ig) G1 monoclonal antibody (mAb) intended to bind circulating human growth differentiation factor 15 (GDF-15), a cytokine involved in cancer-induced cachexia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of adverse events (AEs)	AEs as characterized by incidence, type, frequency, and severity (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE])	From enrollment to the last follow-up visit approximately 60-days post dose
Toxicity	Dose-limiting Toxicity (DLT) events observed at increasing doses of AV-380	While receiving study drug (up to 4 months)
Laboratory Abnormalities	Laboratory abnormalities as characterized by type, frequency, severity (graded according to NCI-CTCAE v5.0) and timing.	From enrollment to the last follow-up visit approximately 60-days post dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum observed plasma concentration for AV-380	From first dose to the last follow-up visit approximately 60-days post dose.
Tmax	Time to reach the Cmax for AV-380	From first dose to the last follow-up visit approximately 60-days post dose
AUC(0-t)	Area under the plasma concentration-time curve from zero time to the last measurable point for AV-380	From first dose to the last follow-up visit approximately 60-days post dose.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Serum levels of Anti-Drug Antibody (ADA) against AV-380 and their potential relationship with AEs and serum levels of GDF-15	From first dose to the last follow-up visit approximately 60-days post dose.
Weight	Change from baseline body weight during the study	From enrollment to the last follow-up visit approximately 60-days post dose.
Patient-Reported Outcomes	Change from baseline in the following questionnaires: Functional Assessment of Anorexia Cachexia Therapy (FAACT); Patient global impression of severity (PGI-S) and patient global impression of change (PGI-C) for appetite, fatigue, and physical activity.	From enrollment to the end of treatment, approximately 4 months
Lumbar (L3) Skeletal Muscle Index (L3SMI)	Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan	From enrollment to the end of treatment, approximately 4 months
Physical Function	Change from baseline in physical function endpoints, including Short Physical Performance Battery test and digital measures of non-sedentary time	From enrollment to the end of treatment, approximately 4 months
Serum level of GDF-15		From enrollment to the last follow-up visit approximately 60-days post dose.
Albumin and CRP	Change from baseline in albumin and CRP levels	From enrollment to the last follow-up visit approximately 60-days post dose.
Tumor status	Evaluate the effect of AV-380 on tumor burden and tumor status, per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)	From enrollment to the last follow-up visit approximately 60-days post dose.
Biomarkers	including activin A and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1] and proinflammatory)	From first dose to the last follow-up visit approximately 60-days post dose.

Collaborators and Investigators

• Sponsor: AVEO Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Loss; Thinness; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cachexia
• Other Study ID Numbers: AV-380-22-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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