Efficacy and Safety Study of F520 Combined With Lenvatinib in the Treatment of Patients With Advanced Solid Tumors

Inclusion Criteria: Phase Ib:

1. Male or female aged ≥18 years and ≤75 years old;
2. Study population: confirmed by histological and/or cytological examination patientswith solid tumors (endometrial cancer, cervical cancer, non-small cell lung cancer,urothelial carcinoma, etc.), patients with metastatic solid tumors who have failed (disease progression or intolerance) after adequate standard treatment or lackeffective treatments;
3. Expected survival period ≥ 12 weeks;
4. ECOG 0-1 points;
5. Blood pressure (BP) is adequately controlled with or without antihypertensive drugs,defined as BP ≤ 150/90 mmHg and unchanged antihypertensive drugs within 1 week priorto enrollment;
6. Vital organ functions meet the following requirements (Reception of granulocytecolony-stimulating factor (G-CSF) or pegylated granulocyte colony-stimulating factor (PEG-G-CSF) or blood transfusion within 14 days prior to laboratory tests is notpermitted for prophylactic use): Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L, hemoglobin (HGB) ≥ 90 g/L,platelet count (PLT) ≥ 75 ×109/L, lymphocyte percentage≥10%; liver function: totalbilirubin level (TBIL)≤1.5×ULN, ALT and AST≤2.5×ULN; if there is liver metastasis, ALTand AST≤5×ULN; Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥40mL/min (Cr>1.5×ULN); Coagulation function: international normalized ratio (INR) ≤1.5×ULN;
7. Aagree to provide archived tumor tissue samples Or fresh tissue samples;
8. Those who understand and voluntarily sign the written informed consent. Phase II:
9. Women aged ≥18 years and ≤75 years old;
10. Study population: Cohort 1: Patients with recurrent or metastatic endometrial cancer (exceptcarcinosarcoma) who have progressed after receiving at least one line of treatment,and the number of previous platinum-containing treatment lines is ≤ 2; Cohort 2:patients with recurrent or metastatic cervical cancer (Squamous cell carcinoma,adenocarcinoma, and adenosquamous carcinoma) who have progressed after receiving atleast one line of platinum-containing regimens and adenosquamous carcinoma); those whoprogressed during or within 6 months after receiving platinum-containing regimenneoadjuvant or adjuvant chemotherapy can also be included;
11. Expected survival ≥ 12 weeks;
12. According to the RECIST1.1 standard, the subject patients must have at least onemeasurable target lesion (extranodal lesions: long diameter ≥ 10mm; intranodallesions: short diameter ≥ 15mm) by enhanced CT and/or enhanced MRI;
13. ECOG 0-1 points;
14. Adequate control of blood pressure (BP) with or without antihypertensive drugs,defined as BP ≤ 150/90 mmHg and antihypertensive drugs remained unchanged within 1week before enrollment;
15. Vital organ functions meet the following requirements (Reception of granulocytecolony-stimulating factor (G-CSF) or pegylated granulocyte colony-stimulating factor (PEG-G-CSF) or blood transfusion within 14 days prior to laboratory tests is notpermitted for prophylactic use): Blood routine: absolute neutrophil count (ANC) ≥ 1.5×109/L, hemoglobin (HGB) ≥ 90 g/L,platelet count (PLT) ≥ 75 ×109/L, lymphocyte percentage≥10%; liver function: totalbilirubin level (TBIL)≤1.5×ULN, ALT and AST≤2.5×ULN; if there is liver metastasis, ALTand AST≤5×ULN; Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥40mL/min (Cr>1.5×ULN); Coagulation function: international normalized ratio (INR) ≤1.5×ULN;
16. Those who agree to provide archived tumor tissue samples or fresh tissue samples;
17. Those who understand and voluntarily sign the written informed consent.

Exclusion Criteria:

1. Those who have received systemic tumor therapy of radiotherapy, chemotherapy,traditional Chinese medicine, hormone therapy, surgery, targeted therapy or antibodydrugs within 28 days (or 5 half-lives of the drug, whichever is shorter) before thefirst dose; Those whose toxicity of previous anti-tumor therapy has not recovered to ≤grade 1 (except alopecia);
2. Those who have previously received any angiogenic drugs that directly target VEGF (Subjects who have only used bevacizumab in the past can be enrolled), anti-PD-1,anti-PD-L1, anti-PD-L2 or any other Antibody or drug therapy that specifically targetsT cell co-stimulation or checkpoint pathways;
3. Subjects with central nervous system (CNS) metastases, unless they have completedlocal therapy (eg, whole brain radiation therapy [WBRT], surgery, or radiosurgery) andhave stopped corticosteroid therapy at least 4 weeks prior to the start of studytreatment;
4. Inability to swallow or disease/surgery significantly affects gastrointestinalfunction, such as malabsorption syndrome, gastrectomy or small bowel resection,bariatric surgery, symptomatic inflammatory bowel disease, etc.;
5. Partial or complete intestinal obstruction or intestinal obstruction occurred within 1month before the first administration;
6. Have suffered from interstitial lung disease, non-infectious pneumonia or uncontrolledlung disease in the past 3 years, including but not limited to pulmonary fibrosis,acute lung disease, etc.;
7. Those with uncontrollable or severe cardiovascular diseases, such as New York HeartAssociation (NYHA) congestive heart failure above grade II, unstable angina,myocardial infarction and other cardiovascular diseases occurring within 6 monthsbefore the first administration;
8. QTcF ≥ 480 milliseconds (QT interval must use Fridericia formula for heart ratecorrection [QTcF]);
9. Within 3 months before the first dose, there were clinically significant hematuria,hematemesis or hemoptysis (>2.5 mL red blood), or other medical history of significantbleeding (such as pulmonary hemorrhage);
10. Those with thrombosis who need treatment in the acute phase;
11. Active hepatitis patients (HBV DNA>2000 IU/mL or 1000 copies of chronic hepatitis B orchronic HBV carriers; HCV positive and HCV-RNA positive hepatitis C patients); humanimmunodeficiency virus (HIV) antibody positive; Treponema pallidum (TP) antibodypositive;
12. Subjects with urine protein>1+ receive 24-hour urine protein quantification, urineprotein ≥1g/24 hours;
13. Those with a known history of contraindications or hypersensitivity to any test drugor any known excipients;
14. Those who have had organ transplantation in the past or received autologous stem celltransplantation within 3 months before the first administration;
15. Those with a history of other malignant tumors within the past 3 years, except locallycurable cancers (radical melanoma, basal or squamous cell carcinoma, carcinoma in situof the bladder or cervix);
16. Immunosuppressant, systemic or local hormone therapy has been used within 14 daysbefore the first administration to achieve the purpose of immunosuppression (dailydose equivalent to prednisone > 10 mg of systemic corticosteroids);
17. Those with a history of drug abuse and alcoholism within 6 months before the firstadministration;
18. Active autoimmune disease requiring systemic treatment within the past 2 years (suchas the use of disease-modifying drugs, corticosteroids, or immunosuppressive drugs),alternative therapy (such as physiological corticosteroid replacement therapy forthyroxine, insulin, or adrenal or pituitary insufficiency, etc.) is not considered asystemic treatment;
19. Those who received (attenuated) live vaccines within 30 days before the firstadministration (except for inactivated influenza vaccines such as injectable seasonalinfluenza vaccines and COVID-19 vaccines);
20. Pregnant or breastfeeding women, female subjects of childbearing age or male subjectswhose partner is a woman of childbearing age do not agree to use highly effectivemethods of contraception during the study period and within 6 months after the laststudy drug treatment;
21. Those judged by the researchers to be unsuitable for enrollment.