efficacy and safety study of f520 combined with lenvatinib in the treatment of patients with advanced solid tumors

Conditions: Solid Tumors

Summary: this is a multicenter, open-label, phase ib/ii study on the efficacy and safety of f520 combined with lenvatinib in the treatment of patients with advanced solid tumors. about 138\~158 patients with advanced solid tumors plan to be enrolled in about 30 study sites of the study. part i: phase ib study evaluating the safety and tolerability of f520 combined with lenvatinib in patients with advanced solid tumors. part ii: phase ii study of f520 combined with lenvatinib in endometrial cancer and cervical cancer.


Eligibility criteria:
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 patients with 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 lack effective 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 prior to enrollment; 6. vital organ functions meet the following requirements (reception of granulocyte colony-stimulating factor (g-csf) or pegylated granulocyte colony-stimulating factor (peg-g-csf) or blood transfusion within 14 days prior to laboratory tests is not permitted 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: total bilirubin level (tbil)≤1.5×uln, alt and ast≤2.5×uln; if there is liver metastasis, alt and 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: 1. women aged ≥18 years and ≤75 years old; 2. study population: cohort 1: patients with recurrent or metastatic endometrial cancer (except carcinosarcoma) 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 at least one line of platinum-containing regimens and adenosquamous carcinoma); those who progressed during or within 6 months after receiving platinum-containing regimen neoadjuvant or adjuvant chemotherapy can also be included; 3. expected survival ≥ 12 weeks; 4. according to the recist1.1 standard, the subject patients must have at least one measurable target lesion (extranodal lesions: long diameter ≥ 10mm; intranodal lesions: short diameter ≥ 15mm) by enhanced ct and/or enhanced mri; 5. ecog 0-1 points; 6. adequate control of blood pressure (bp) with or without antihypertensive drugs, defined as bp ≤ 150/90 mmhg and antihypertensive drugs remained unchanged within 1 week before enrollment; 7. vital organ functions meet the following requirements (reception of granulocyte colony-stimulating factor (g-csf) or pegylated granulocyte colony-stimulating factor (peg-g-csf) or blood transfusion within 14 days prior to laboratory tests is not permitted 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: total bilirubin level (tbil)≤1.5×uln, alt and ast≤2.5×uln; if there is liver metastasis, alt and 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; 8. those who agree to provide archived tumor tissue samples or fresh tissue samples; 9. 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 antibody drugs within 28 days (or 5 half-lives of the drug, whichever is shorter) before the first 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 targets t cell co-stimulation or checkpoint pathways; 3. subjects with central nervous system (cns) metastases, unless they have completed local therapy (eg, whole brain radiation therapy \[wbrt\], surgery, or radiosurgery) and have stopped corticosteroid therapy at least 4 weeks prior to the start of study treatment; 4. inability to swallow or disease/surgery significantly affects gastrointestinal function, 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 1 month before the first administration; 6. have suffered from interstitial lung disease, non-infectious pneumonia or uncontrolled lung 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 heart association (nyha) congestive heart failure above grade ii, unstable angina, myocardial infarction and other cardiovascular diseases occurring within 6 months before the first administration; 8. qtcf ≥ 480 milliseconds (qt interval must use fridericia formula for heart rate correction \[qtcf\]); 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 significant bleeding (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 or chronic hbv carriers; hcv positive and hcv-rna positive hepatitis c patients); human immunodeficiency virus (hiv) antibody positive; treponema pallidum (tp) antibody positive; 12. subjects with urine protein\>1+ receive 24-hour urine protein quantification, urine protein ≥1g/24 hours; 13. those with a known history of contraindications or hypersensitivity to any test drug or any known excipients; 14. those who have had organ transplantation in the past or received autologous stem cell transplantation within 3 months before the first administration; 15. those with a history of other malignant tumors within the past 3 years, except locally curable cancers (radical melanoma, basal or squamous cell carcinoma, carcinoma in situ of the bladder or cervix); 16. immunosuppressant, systemic or local hormone therapy has been used within 14 days before the first administration to achieve the purpose of immunosuppression (daily dose equivalent to prednisone \> 10 mg of systemic corticosteroids); 17. those with a history of drug abuse and alcoholism within 6 months before the first administration; 18. active autoimmune disease requiring systemic treatment within the past 2 years (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressive drugs), alternative therapy (such as physiological corticosteroid replacement therapy for thyroxine, insulin, or adrenal or pituitary insufficiency, etc.) is not considered a systemic treatment; 19. those who received (attenuated) live vaccines within 30 days before the first administration (except for inactivated influenza vaccines such as injectable seasonal influenza vaccines and covid-19 vaccines); 20. pregnant or breastfeeding women, female subjects of childbearing age or male subjects whose partner is a woman of childbearing age do not agree to use highly effective methods of contraception during the study period and within 6 months after the last study drug treatment; 21. those judged by the researchers to be unsuitable for enrollment.

Keywords: f520 pd-1