Apatinib Plus Sintilimab in Advanced Gastric Cancer Refractory to at Least Two Previous Chemotherapy Regimens

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of Apatinib combined with PD-1 antibody Sintilimab for for Chemotherapy-Refractory Advanced Metastatic Gastric Cancer

Detailed Description
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Patients with advanced gastric cancer (AGC) can be treated with multiple lines of chemotherapy. After second-line treatment some patients may receive third- and subsequent lines of chemotherapy if their performance status is well-preserved and they are willing to receive subsequent active treatments. Apatinib is a small-molecule VEGFR-2 tyrosine kinase inhibitor approved by the CFDA for the treatment of advanced gastric cancer. In a phase III trial, apatinib significantly improved PFS and OS compared with placebo, but the clinical benefit was modest. As a result of toxicity, 850 mg/day Apatinib may cause dose reduction and delay in some patients ,which also caused some doubts. Therefore, it is a reasonable treatment strategy by reducing the dose and combining it with another low-toxic drug to achieve similar or better effects. Some studies have shown that the combination of targeted therapy and immunotherapy may be effective in solid tumor. Sintilimab (IBI308) is a monoclonal antibody targeting programmed death-1 (PD-1). So, the investigators designed an open-label, single-arm, phase II clinical study to evaluate the efficacy and safety of apatinib combined with Sintilimab in Chemotherapy-Refractory Advanced Metastatic Gastric Cancer.

Official Title
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Apatinib Plus Sintilimab in Patients With Advanced Gastric Cancer

Conditions
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Advanced Metastatic Gastric Cancer

Intervention / Treatment
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* Drug: Apatinib Mesylate
* Drug: Sintilimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20-75 years old Has histologically confirmed diagnosis of unresectable locally advanced,recurrent or metastatic gastric or GEJ adenocarcinoma Life expectancy of more than 3 months Eastern Cooperative Oncology Group (ECOG) performance status was 0 - 1 Have failed for at least 2 lines of chemotherapy At least 3 weeks from previous chemotherapy at first dose of trial drug Resolution of all acute toxic side effects of prior therapy or surgical procedures to grade ≤ 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTC) (except for the laboratory values) Failure of prior palliative chemotherapy/chemotherapies (at least one irinotecan- or cisplatin-based). Failure is defined either by progression of disease or by significant toxicity that precludes further treatment. At least one measurable lesion defined by RECIST 1.1 as determined by investigator assessment. Has adequate organ function At least 4 weeks from any major surgery (at first dose of trial drug) Patients must be able to swallow apatinib Exclusion Criteria: In the past, participants have received anti PD-1, anti PD-L1 or anti PD-L2 drugs or drugs targeting another stimulation or synergistic inhibition of T cell receptors (such as Cytotoxic T-Lymphocyte Antigen 4 [CTLA-4] and CD137) Other co-existing malignancies or malignancies diagnosed within the last 5 years(except cured cutaneum carcinoma or carcinoma in situs of cervix) Less than 4 weeks from the last clinical trial Active and uncontrollable bleeding from gastrointestinal tract Known history of QT interval prolongation, ongoing QT prolongation (> 450 msec for males or > 470 msec for females), any cardiac ventricular dysrhythmias, atrial fibrillation of any grade Hypertension that cannot be controlled by medications (> 140/90 mmHg despite optimal medical therapy) Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed; Factors that could have an effect on oral medication (such as inability to swallow, chronic diarrhea and intestinal obstruction); Active uncontrolled infection Known human immunodeficiency virus (HIV) infection Symptomatic central nervous metastasis and/or cancerous meningitis Known allergic/hypersensitivity reaction to any of the components of the treatment; or known drug abuse/alcohol abuse Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apatinib+Sintilimab<br>Apatinib 500mg qd p.o and Sintilimab 200mg intravenously on day 1 every 3 weeks until disease progression or intolerable toxicity or patients withdrawal of consent | Drug: Apatinib Mesylate<br>* Apatinib 500mg qd, oral, taken half an hour after a meal<br>* Other names: Apatinib;Drug: Sintilimab<br>* Sintilimab 200mg intravenously on day 1<br>* Other names: IBI308;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate(DCR) | The percentage of patients who have achieved complete response, partial response and stable disease,evaluated by RECIST, confirmed at least 4 weeks following the date of the initial response. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The percentage of patients who achieve complete response or partial response,evaluated by RECIST, confirmed at least 4 weeks following the date of the initial response. | 12 months | 
| Overall survival (OS) | Overall survival (OS) was calculated from the date of initial treatment with apatinib to the date of death due to any cause. | up to 12 months | 
| Duration of Response (DOR) | Time from date of first RECIST response to progressive disease [PD] or death | up to 12 months | 
| Progression Free Survival (PFS) | PFS was calculated from the day of randomization to the date of first documented progression, or death from any cause. | up to 12 months | 
| Adverse events（AE） | Adverse events assessed using the NCI common toxicity criteria, version 4.01 | up to 12 months |