Overview

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.

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.