Clinical Trials

Inclusion Criteria:

• Dose Expansion: Histologically confirmed and documented, previously untreated or treated stage IIIB or IV Non-Small Cell Lung Cancer (NSCLC) having failed no more than 1 previous platinum containing chemotherapy regimen for locally advanced or metastatic disease or relapsed/refractory locally advanced or metastatic gastric adenocarcinoma having failed no more than 2 previous chemotherapy regimen for locally advanced or metastatic disease. Subjects with NSCLC who are known to be epidermal growth factor receptor (EGFR)-mutation positive must have received an EGFR inhibitor and subjects known to be anaplastic lymphoma kinase (ALK)-mutation positive must have received an ALK inhibitor.

Prior to enrollment, confirmation of the following must be obtained:

• Dose expansion - For subjects in the dose expansion portion of the study, it is mandatory that available archived tumor tissue in FFPE block or minimum 10 unstained consecutive core biopsy slides from 1 archival block that meet specific tissue requirements are available.

• One or more tumors measurable on CT scan/MRI scan per RECIST v 1.1. - Previously irradiated tumors may be eligible if they have clearly progressed in size.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy ≥3 months.

Subjects must also satisfy the following inclusion criterion:

• Subjects (NSCLC and gastric adenocarcinoma) must be determined to have HA-high levels from their tumor biopsies.
• NSCLC and gastric adenocarcinoma subjects must have tissue available for HA-selection and PD-L1 testing.

Exclusion Criteria:

• Previous treatment with pembrolizumab, nivolumab, or other programmed cell death-1 antibody (anti- PD-1) or PD-1 ligand-antibody (anti-PD-L1) agents.
• New York Heart Association Class III or IV (Appendix D) cardiac disease or myocardial infarction within the past 12 months before screening, or preexisting atrial fibrillation.
• Prior history of cerebrovascular accident or transient ischemic attack.
• NSCLC subjects with known brain metastases (certain exceptions allowed)
• Gastric adenocarcinoma subjects with brain metastases
• History of active bleeding within the last 3 months requiring transfusion
• Anti-angiogenic therapy within the last month
• Patients with known interstitial fibrosis or interstitial lung disease.
• Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
• History of:
  1. Pneumonitis that requires oral or IV steroids;
  2. Or known cases of hepatobiliary diseases (e.g., primary biliary cholangitis, primary sclerosing cholangitis, history of immune-mediated cholangitis);
     • Subjects with cholangitis attributed to infectious etiology (e.g., ascending cholangitis, bacterial cholangitis) are eligible if the infection has been fully resolved prior to the screening visit.
  3. Or known cases of drug-induced hepatobiliary toxicities.
• Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents.
• History of another primary cancer within the last 3 years that required treatment, with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in situ.