apatinib plus sintilimab in advanced gastric cancer refractory to at least two previous chemotherapy regimens

Conditions: Advanced Metastatic Gastric Cancer

Summary: 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

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.

Eligibility criteria:
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