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

Sponsor

AVEO Pharmaceuticals, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05865535

Collaborator

(none)

Enrollment

Arms

22.5

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cachexia	Biological: AV-380	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

May 16, 2023

Anticipated Primary Completion Date :

Nov 18, 2024

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 IV infusion of AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.	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.
Experimental: Cohort 2 IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.	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.
Experimental: Cohort 3 IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.	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.
Experimental: Cohort 4 IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.	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.
Experimental: Cohort 5 IV infusion AV-380. This cohort will proceed at a new dose level with approval of the Dose Escalation Committee, after evaluation of data from the previous cohort. IV infusion AV-380. 7 doses will be given -- the 2nd dose will be 28 days after the first dose, the remaining 5 doses will be given every 2 weeks.	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.

Outcome Measures

Primary Outcome Measures

Assessment of adverse events (AEs) [Through 90 days post last dose]
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)
Cmax [Up to 4 months]
Maximum Observed Plasma Concentration for AV-380
Serum level of GDF-15 [Through 90 days post last dose]
Tmax [Up to 4 months]
Time to Reach the Cmax for AV-380
AUC(0-t) [Up to 4 months]
Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for AV-380

Secondary Outcome Measures

Weight and body mass index (BMI) [Through 90 days post last dose]
Immunogenicity [Up to 4 months]
Serum levels of Anti-Drug Antibody (ADA) against AV-380
6-minute walk test [Through 60 days post last dose]
Assess aerobic capacity and endurance by measuring the distance covered over a time of 6 minutes
Metabolic Vulnerability Index (MVX) [Through 60 days post last dose]
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.
Handgrip test [Through 60 days post last dose]
Handgrip strength test to measure the maximum isometric strength of the hand and forearm muscles
L3 Skeletal Muscle Index (L3SMI) [Through 60 days post last dose]
Measurement of a cross-sectional area of muscle at the level of the third lumbar vertebra (L3) using computed tomography (CT) scan
Lean body mass (LBM) [Through 60 days post last dose]
The difference between total body mass and fat mass

Other Outcome Measures

Best objective response (BOR) [Through 90 days post last dose]
defined as the proportion of patients who have a complete response (CR) or partial response (PR) as determined by the Investigator
Biomarkers [Through 60 days post last dose]
including activin and cytokine levels (e.g., monocyte chemoattractant protein-1 [MCP-1])

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient must be ≥ 18 years of age at the time of signing the informed consent.
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:
CRC patients who are receiving FOLFOX/FOLFOXIRI ± bevacizumab
Pancreatic cancer patients who are receiving FOLFOX/FOLFIRINOX
Patients with cachexia as defined by Fearon criteria:
Weight loss > 5% over past 6 months (in absence of simple starvation), or
BMI < 20 kg/m2 and any degree of weight loss > 2%, or
Sarcopenia and any degree of weight loss > 2%
Patients with life expectancy ≥ 3 months

Exclusion Criteria:

Significant clinical manifestation of any allergic, dermatological, hepatic, renal, hematological, pulmonary, metabolic, cardiovascular, gastrointestinal, neurological, or psychiatric disorders (e.g., anorexia nervosa).
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.
Significant cardiovascular disease, including myocardial infarction within 3 months prior to start of protocol therapy.
Corrected QT interval calculated by the Fridericia formula (QTcF) > 460 ms within the Screening period prior to the first dose of study treatment.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

AVEO Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

AVEO Pharmaceuticals, Inc.

ClinicalTrials.gov Identifier:

NCT05865535

Other Study ID Numbers:

AV-380-22-102

First Posted:

May 19, 2023

Last Update Posted:

May 19, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasm Metastasis

Wasting Syndrome

Cachexia

Study Results

No Results Posted as of May 19, 2023