Clinical trial NCT05865535: A Dose Escalation Study of AV-380 in Cancer Patients With Cachexia
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cachexia
Lead sponsor: AVEO Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of adverse events (AEs)
timeFrame: From enrollment to the last follow-up visit approximately 60-days post dose
measure: Toxicity
timeFrame: While receiving study drug (up to 4 months)
measure: Laboratory Abnormalities
timeFrame: From enrollment to the last follow-up visit approximately 60-days post dose.
Secondary outcomes:
measure: Cmax
timeFrame: From first dose to the last follow-up visit approximately 60-days post dose.
measure: Tmax
timeFrame: From first dose to the last follow-up visit approximately 60-days post dose
measure: AUC(0-t)
timeFrame: From first dose to the last follow-up visit approximately 60-days post dose.
Other outcomes:
measure: Immunogenicity
timeFrame: From first dose to the last follow-up visit approximately 60-days post dose.
measure: Weight
timeFrame: From enrollment to the last follow-up visit approximately 60-days post dose.
measure: Patient-Reported Outcomes
timeFrame: From enrollment to the end of treatment, approximately 4 months
measure: Lumbar (L3) Skeletal Muscle Index (L3SMI)
timeFrame: From enrollment to the end of treatment, approximately 4 months
measure: Physical Function
timeFrame: From enrollment to the end of treatment, approximately 4 months
measure: Serum level of GDF-15
timeFrame: From enrollment to the last follow-up visit approximately 60-days post dose.
measure: Albumin and CRP
timeFrame: From enrollment to the last follow-up visit approximately 60-days post dose.
measure: Tumor status
timeFrame: From enrollment to the last follow-up visit approximately 60-days post dose.
measure: Biomarkers
timeFrame: From first dose to the last follow-up visit approximately 60-days post dose.
Locations:
city: Beverly HIlls
country: United States
facility: Beverly Hills Cancer Center
state: California
city: Lakewood
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Orlando
country: United States
facility: Advent Health Orlando Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Shirley
country: United States
facility: New York Cancer And Blood Specialists
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Henry-Joyce Cancer Clinic
state: Tennessee
city: Kingwood
country: United States
facility: Community Clinical Trials
state: Texas
Study officials:
References: