Clinical trial NCT05740215: Efficacy and Safety Study of F520 Combined With Lenvatinib in the Treatment of Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Keywords: F520
PD-1
Lead sponsor: Shandong New Time Pharmaceutical Co., LTD
Sponsor class: INDUSTRY
First posted: 2023-02-22
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Serious adverse events
timeFrame: 21 days after first dose
measure: Adverse events
timeFrame: 21 days after first dose
measure: Dose-limiting toxicity (DLT)
timeFrame: 21 days after first dose
measure: Maximum tolerated dose (MTD)
timeFrame: 21 days after first dose
measure: Phase II recommended dose (RP2D).
timeFrame: 21 days after first dose
measure: Objective Response Rate (ORR)
timeFrame: 24 weeks
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: through study completion, an average of 2 year
measure: Maximum Plasma Concentration (Cmax）
timeFrame: 30 days (±7 days) after the last dose, early withdrawal or occurrence of SAE or grade ≥ 3 TRAE related to the study drug
measure: Objective response rate (ORR)
timeFrame: 24 weeks
measure: PFS
timeFrame: through study completion, an average of 2 year
measure: PFS
timeFrame: through study completion, an average of 2 year
measure: Adverse events
timeFrame: 30 days after the last dose
measure: Adverse reactions
timeFrame: 30 days after the last dose
measure: Serious adverse events
timeFrame: 30 days after the last dose
measure: Severe adverse reactions
timeFrame: 30 days after the last dose
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
Study officials:
References: