Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma

Inclusion Criteria:

• Diagnosis: Histologically confirmed gastric/esophagealgastric adenocarcinoma,recurrent, locally advanced or metastatic, PD-L1-positive disease (CPS ≥1),progressed on at least two prior lines of therapy and/or discontinued second linetherapy for intolerance, indicated for Keytruda therapy. OR: Hepatocellularcarcinoma with diagnosis confirmed by histologic or cytologic analysis or clinicalfeatures according to the American Association for the Study of Liver Diseasescriteria for patients with cirrhosis, unresectable disease not amenable tolocoregional therapy with disease progression after at least one prior line ofsystemic therapy or discontinued first line therapy for intolerance.

• At least 1 measurable metastatic lesion that has not been irradiated. The lesionwill be measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), and be documented by radiological evaluation within 28 days prior toregistration. For subjects with locally advanced disease: at least one measurablelesion that has not been irradiated, documented by radiological evaluation within 28days prior to registration.

• Any prior radiation therapy must be completed at least 28 days prior to the firstdose of study treatment.

• Eighteen years of age or older.

• Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2.

• Adequate bone marrow, liver, and renal function

• Negative urine or serum pregnancy test for women of childbearing potential.

• Women and men of childbearing potential must agree to use adequate contraceptionprior to registration, for the duration of study participation and until 4 monthsafter the last study drug dosing.

• Able to swallow tablets and agree to take the prescribed tablets twice daily.

Exclusion Criteria:

• Clinical or radiographic evidence of current brain metastasis. History of treatedbrain metastases is allowable.

• Cardiac disease

• Uncontrolled hypertension

• Severe hemorrhage/bleeding event within 28 days prior to the first dose of studytreatment

• Major surgery, open biopsy, or significant traumatic injury within 42 days prior tothe first dose of study treatment

• Current serious, nonhealing wound, ulcer, or bone fracture within 42 days prior tothe first dose of study treatment

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominalabscess within 6 months prior to the first dose of study treatment.

• Presence of an uncontrolled infection or infection that required intravenousantibiotics, antifungals, or antivirals within 14 days prior to the first dose ofstudy treatment.

• Known human immunodeficiency virus (HIV) infection. HIV-infected subjects oneffective anti-retroviral therapy are eligible if the most recent viral load testperformed within six months of screening (based on medical chart review) isnegative. The safety of telatinib in this subject population has not been studied.

• Known chronic hepatitis B, unless receiving antiviral treatment.

• Known Child-Pugh Score B or C liver cirrhosis.

• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any otherform of immunosuppressive therapy within 7 days prior to the first dose of studytreatment or has been diagnosed with an autoimmune disease that has requiredsystemic treatment in the past 2 years (i.e., with use of disease modifying agents,corticosteroids, or immunosuppressive drugs). Patients that require replacementtherapy (e.g., thyroxine [T4], insulin, or physiologic corticosteroid replacementtherapy for adrenal or pituitary insufficiency, etc.) may be enrolled.

• History of (non-infectious) pneumonitis that required steroids, or currentpneumonitis, or has a history of interstitial lung disease.

• Has received a live-virus vaccination within 30 days of planned treatment start.

• Known history of proteinuria > 1gr/24 hours.

• Previous or concurrent cancer that is distinct in primary site or histology from thecurrent stomach or liver cancer. Subjects with cervical cancer in-situ, treatedbasal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancercuratively treated are not excluded.

• Anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery,immunotherapy, biologic therapy, or tumor embolization) or investigational agentwithin 28 days prior to the first dose of study treatment.

• Known or suspected allergy to any component of telatinib or Keytruda

• Prior or current history of substance abuse, or medical, psychological, or socialcondition that in the opinion of the investigator may interfere with the subject'sparticipation in the study or evaluation of the study result.

• Women who are pregnant or breastfeeding.

• Prior history of thromboembolic disease, e.g., deep vein thrombosis (DVT), pulmonaryemboli (PE), within 6 months prior to the first dose of study treatment that hasrequired continued medical intervention.

• Baseline peripheral neuropathy.