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

Cachexia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05865535
• Other study ID #: AV-380-22-102
• Status: Recruiting
• Phase: Phase 1
• Start date: June 13, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2024
• Source: AVEO Pharmaceuticals, Inc.
• Contact: AVEO Clinical Trials Office
• Phone: (857)400-0101
• Email: clinical[@]aveooncology.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This open label ascending dose study is designed to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AV-380 in metastatic 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 30, 2025
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient must be = 18 years of age at the time of signing the informed consent.

2. Patients with histologically confirmed metastatic CRC or pancreatic cancer, who are actively receiving SoC chemotherapy in the first line setting for metastatic disease;

eligible patients must have completed at least 2 Cycles of chemotherapy to eligible:

1. CRC patients who are receiving FOLFOX/FOLFOXIRI ± bevacizumab

2. Pancreatic cancer patients who are receiving FOLFOX/FOLFIRINOX

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. Significant clinical manifestation of any allergic, dermatological, hepatic, renal, hematological, pulmonary, metabolic, cardiovascular, gastrointestinal, neurological, or psychiatric disorders (e.g., anorexia nervosa).

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. Significant cardiovascular disease, including myocardial infarction within 3 months prior to start of protocol therapy.

4. Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within the Screening period prior to the first dose of study treatment.

Related Conditions & MeSH terms

• Cachexia
• Neoplasm Metastasis

Intervention

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.

Locations

Country	Name	City	State
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	New York Cancer And Blood Specialists	Babylon	New York
United States	North Shore Hematology Oncology Associates P.C. dba NY Cancer and Blood Specialists	Bronx	New York
United States	MUSC Hollings Cancer Center	Charleston	South Carolina
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Piedmont Cancer Institute	Fayetteville	Georgia
United States	New York Cancer and Blood Specialists	New York	New York
United States	Piedmont Cancer Institute	Newnan	Georgia
United States	Advent Health Orlando Hospital	Orlando	Florida
United States	New York Cancer And Blood Specialists	Patchogue	New York
United States	New York Cancer and Blood Specialists	Port Jefferson Station	New York
United States	New York Cancer And Blood Specialists	Riverhead	New York
United States	Medical Oncology Associates	Spokane	Washington
United States	Medical Oncology Associates	Spokane Valley	Washington
United States	Piedmont Cancer Institute	Stockbridge	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
AVEO Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Best objective response (BOR)	defined as the proportion of patients who have a complete response (CR) or partial response (PR) as determined by the Investigator	Through 90 days post last dose
Other	Biomarkers	including activin and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1])	Through 60 days post last dose
Primary	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] v5.0)	Through 90 days post last dose
Primary	Cmax	Maximum Observed Plasma Concentration for AV-380	Up to 4 months
Primary	Serum level of GDF-15		Through 90 days post last dose
Primary	Tmax	Time to Reach the Cmax for AV-380	Up to 4 months
Primary	AUC(0-t)	Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for AV-380	Up to 4 months
Secondary	Weight and body mass index (BMI)		Through 90 days post last dose
Secondary	Immunogenicity	Serum levels of Anti-Drug Antibody (ADA) against AV-380	Up to 4 months
Secondary	6-minute walk test	Assess aerobic capacity and endurance by measuring the distance covered over a time of 6 minutes	Through 60 days post last dose
Secondary	Metabolic Vulnerability Index (MVX)	The MVX is a blood test that combines results from analytes that represent metabolic malnutrition (MMX; valine, leucine, isoleucine, citrate) and inflammation (IFX; GlycA and S-HDLP) to provide a single prognostic score (1-100) for risk of death.	Through 60 days post last dose
Secondary	Handgrip test	Handgrip strength test to measure the maximum isometric strength of the hand and forearm muscles	Through 60 days post last dose
Secondary	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	Through 60 days post last dose
Secondary	Lean body mass (LBM)	The difference between total body mass and fat mass	Through 60 days post last dose