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

Study Overview
=================
Brief Summary
-----------------
This is a phase II, single arm, open-label study of two parallel cohorts (advanced stomach and gastroesophageal junction cancer and hepatocellular carcinoma), evaluating the effects of telatinib in combination with Keytruda on progression-free survival.

Official Title
-----------------
A Phase II Study Evaluating Safety and Efficacy of Telatinib in Combination With Keytruda in Subjects With Advanced Stomach and Gastroesophageal Junction Cancers or Hepatocellular Carcinoma

Conditions
-----------------
Gastric Cancer, Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: Telatinib
* Drug: Keytruda


Participation Criteria
=================
Eligibility Criteria
-----------------
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 line therapy for intolerance, indicated for Keytruda therapy. OR: Hepatocellular carcinoma with diagnosis confirmed by histologic or cytologic analysis or clinical features according to the American Association for the Study of Liver Diseases criteria for patients with cirrhosis, unresectable disease not amenable to locoregional therapy with disease progression after at least one prior line of systemic therapy or discontinued first line therapy for intolerance. At least 1 measurable metastatic lesion that has not been irradiated. The lesion will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), and be documented by radiological evaluation within 28 days prior to registration. For subjects with locally advanced disease: at least one measurable lesion that has not been irradiated, documented by radiological evaluation within 28 days prior to registration. Any prior radiation therapy must be completed at least 28 days prior to the first dose 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 contraception prior to registration, for the duration of study participation and until 4 months after 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 treated brain metastases is allowable. Cardiac disease Uncontrolled hypertension Severe hemorrhage/bleeding event within 28 days prior to the first dose of study treatment Major surgery, open biopsy, or significant traumatic injury within 42 days prior to the first dose of study treatment Current serious, nonhealing wound, ulcer, or bone fracture within 42 days prior to the first dose of study treatment History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first dose of study treatment. Presence of an uncontrolled infection or infection that required intravenous antibiotics, antifungals, or antivirals within 14 days prior to the first dose of study treatment. Known human immunodeficiency virus (HIV) infection. HIV-infected subjects on effective anti-retroviral therapy are eligible if the most recent viral load test performed within six months of screening (based on medical chart review) is negative. 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 other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment or has been diagnosed with an autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Patients that require replacement therapy (e.g., thyroxine [T4], insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled. History of (non-infectious) pneumonitis that required steroids, or current pneumonitis, 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 the current stomach or liver cancer. Subjects with cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancer curatively treated are not excluded. Anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) or investigational agent within 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 social condition that in the opinion of the investigator may interfere with the subject's participation 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), pulmonary emboli (PE), within 6 months prior to the first dose of study treatment that has required continued medical intervention. Baseline peripheral neuropathy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: telatinib + Keytruda<br> | Drug: Telatinib<br>* 900mg by mouth twice daily until disease progression, intolerable toxicities, or withdrawal of consent<br>Drug: Keytruda<br>* 200mg intravenous infusion every three weeks until disease progression, intolerable toxicities, or withdrawal of consent<br>* Other names: pembrolizumab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Duration of time from start of treatment until progression or death, whichever comes first | from the start of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | The percentage of patients who have a partial or complete response to treatment | from the start of treatment until the end of treatment, approximately 12 months | 
| Disease control rate | The percentage of patients who have stable disease, partial response, or complete response to treatment | from the start of treatment until the end of treatment, approximately 12 months | 
| Overall survival | The length of time from the start of treatment that patients are still alive | from the start of treatment until the end of follow-up, approximately 18 months | 
| Incidence and severity of adverse events | Incidence and severity of adverse events as measured by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5 | from the start of treatment until 30 days following the end of treatment or until initiation of a new anticancer therapy (whichever occurs first), approximately 13 months |