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

• Status: Recruiting
• Trial end date: 2024-05-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shandong New Time Pharmaceutical Co., LTD
• Treatments: Lenvatinib

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.