A Phase 1b/2 Study of YL-13027 Combined With Sintilimab in Patients With Advanced Solid Tumors

Inclusion Criteria:

1. Males and/or females age from 18 to 75.
2. Histologically or cytologically confirmed patients with advanced malignant solidtumors, extracranial solid tumors must be malignant tumors, including but not limitedto lung cancer, head and neck cancer, renal clear cell carcinoma, urinary epithelialcarcinoma, chordoma, etc. Intracranial primary tumors include malignant tumors andsome benign tumors lacking effective standard treatment after current recurrence,including but not limited to glioma, meningioma, ependymoma, craniopharyngioma,refractory pituitary tumor, etc. Eligible patients must have failed standardtreatment, have no standard treatment, have refused standard treatment, or have beendetermined by the investigator to be unsuitable for standard treatment at this stage.
3. At least 1 measurable lesion according to tumor assessment criteria.
4. Eastern Cooperative Oncology Group performance status of 0 to 2.
5. Life expectancy of at least 3 months.
6. Acceptable organ function: Absolute neutrophil count(ANC)≥1.5×109/L, Plateletcount(PLT)≥100×109/L, Hemoglobin(Hb)≥90 g/L, Total bilirubin(TBIL)≤1.5×Upper limit ofnormal value(ULN), Alanine aminotransferase(ALT)≤2.5×ULN, Aspartateaminotransferase(AST)≤2.5×ULN, Creatinine(Cr)≤1.5×ULN, Creatinine clearance ≥50ml/min,Left Ventricular Ejection Fractions(LVEF)≥50%, QTcF<450 ms.
7. The washout period from the last time accepting any anti-tumor treatment (includingchemotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy,tumor embolization) to participating in this test should be 3 weeks or more.Thewashout period of oral fluorouracil should be 2 weeks or more, and that of mitomycinand nitrosocarbamide should be 6 weeks or more.The washout period of drugs withanti-tumor angiogenic effects (those targeting VEGF, VEGF receptors including, but notlimited to bevacizumab, anlotinib, apatinib, furquinib, lenvatinib, sorafenib,regorafenib, etc.) should be 8 weeks or more. The washout period of other anti-tumortreatments (radiotherapy, treatment with other test drugs) should be 4 weeks or more.
8. Fertile male and female must agree to use medically approved contraceptives during thestudy and within 6 months after the last dose of the study.
9. Blood pregnancy test of female who is capable of conceivingshould be negative 7 daysbefore the first dose.Patients cannot breastfeed.If the patient has stoppedbreastfeeding at the time of study entry, the cessation of breastfeeding must be fromthe day of first dose to more than 30 days after the last dose.
10. The last time participate in an investigational drug study should be more than onemonth prior to the study entry.
11. According to the judgment of the investigator, the patient has high compliance and iswilling to complete the experiment and comply with the protocol.
12. Voluntary participation in this clinical trial, understanding of the study proceduresand the ability to sign informed consent forms (ICFs).

Exclusion Criteria:

1. There is third interstitial effusion (such as massive pleural effusion and ascites)which can not be controlled by drainage or other methods.
2. Within 3 months before the first dose, grade 3 or grade 4 gastrointestinal bleeding orvaricose bleeding and requiring blood transfusion or endoscopic or surgicalintervention has happened.
3. Medical history of difficulty in swallowing, malabsorption, or other chronicgastrointestinal disease, or conditions that may hamper compliance and/or absorptionof the tested product.
4. Patients with a definitely history of neurological or psychiatric disorders.
5. Known infection with human immunodeficiency virus (HIV), hepatitis B virus(HBV), orhepatitis C virus (HCV).
6. History of immunodeficiency, including HIV positive test, other acquired or congenitalimmunodeficiency disorders, organ transplantation or allogeneic bone marrowtransplantation.
7. Exists moderate or severe heart disease: (1) Within 6 months before the firstdose,myocardial infarction, angina, grade II/III/IV congestive heart failure,pericardial effusion, uncontrollable severe hypertension (up to 150/90 mmHg or more) . (2) ECG abnormalities with clinical significance: symptomatic or persistent atrial orventricular arrhythmias, degree II or III atrioventricular block, bundle branch block. (3) The echocardiogram shows significant abnormalities: For example, moderate orsevere heart valve function defects are assessed according to the normal lower limitof the institution;Patients with minor or mild valve regurgitation (tricuspid,pulmonary, mitral, or aortic) can be included in this study. (4) Laboratoryexamination shows troponin T levels increasing. (5) Various factors that may increasethe risk of QTcF prolonging or arrhythmia events. (6) Predisposition factors cause thedevelopment of ascending aorta or aortic arch aneurysm: For example, marfan syndrome,CT records of the history of cardiac vascular injury. (7) History of heart or aorticsurgery.
8. Intracerebral lesions with significant space occupying effects (needing Dehydrationtreatment, glucocorticoid treatment or diuretic treatment)，spinal cord or pia materdissemination.
9. At the beginning of the study, the unrecovered toxicity of the previous treatmentexceeded CTCAE5.0 grade 1(except for hair loss).
10. According to the judgement of the researcher,there are concomitant diseases thatseriously endanger the safety of patients or affect the completion of the study (suchas severe hypertension, diabetes, thyroid diseases, etc.).
11. Patients has received vaccines other than inactivated vaccine within 30 days beforeenrollment.
12. The investigator considers that the patient has other reasons for not being suitableto participate in this study.