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This is a multicenter, randomized, open-label Phase II/III clinical study, aiming to evaluate the efficacy and safety of LB1410 in combination with lenvatinib (whether in combination with LB4330)versus the chemotherapy regimen selected by the investigators for patients with advanced recurrent/metastatic cervical cancer.
This study is an open-label, multicenter Phase II/III clinical trial in advanced/metastatic cervical cancer to evaluate the antitumor efficacy, safety, tolerability, pharmacokinetics (PK), and biomarkers of LB1410 in combination with lenvatinib, with or without LB4330.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: LB1410 + Lenvatinib | Experimental | LB1410 (intravenous, Q2W) with lenvatinib (oral, QD),up to 2 years |
|
| Cohort 2: LB1410 + LB4330 + Lenvatinib | Experimental | LB1410 (IV, Q2W for up to 2 years), LB4330 (IV, Q2W for 4 cycles), and lenvatinib (oral, once daily for up to 2 years) |
|
| Cohort 3: LB1410 | Experimental | LB1410 (IV, Q2W for up to 2 years) |
|
| Cohort 4: LB1410 + LB4330 | Experimental | LB1410 (IV, Q2W for up to 2 years) plus LB4330 (IV, Q2W for 4 cycles) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LB1410 | Biological | LB1410 (IV, Q2W for up to 2 years) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) assessed by an Independent Radiology Review Committee (IRRC) | defined as the percentage of patients with a best overall response of Complete Response or Partial Response per RECIST 1.1. | Approximately 24 months |
| Duration of Response (DOR) assessed by an Independent Radiology Review Committee (IRRC) | defined as the time from the first documented response (CR or PR) to the first documented disease progression or death due to underlying cancer per RECIST 1.1. | Approximately 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) assessed by the investigator | defined as the percentage of patients with a best overall response of Complete Response or Partial Response per RECIST 1.1. | Approximately 24 months |
| Duration of Response (DOR) assessed by the investigator |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarker(TIM3) | Correlation between TIM3 expression and clinical efficacy endpoints (ORR, DCR, PFS, OS) as assessed by the investigator according to RECIST 1.1 criteria. | Until end of study,approximately 24 months |
| Biomarker(PD-L1) |
Inclusion Criteria
Exclusion Criteria
For cohorts containing lenvatinib, patients meeting any of the following criteria are ineligible:
Pregnant or breastfeeding women.
History of ≥Grade 3 immune-related adverse events (irAEs) during prior immunotherapy.
Active autoimmune disease or symptomatic autoimmune disease.
Any of the following prior treatments:
Positive HIV test, active syphilis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection.
Other malignancies within the past 3 year.
Leptomeningeal metastasis, spinal cord compression, symptomatic or unstable brain metastases.
Uncontrolled or poorly controlled diabetes.
Arterial/venous thrombotic events within 6 months.
Clinically significant and unstable pleural, peritoneal, or pericardial effusion.
Known interstitial lung disease.
Prior use of drugs with the same mechanism as this study (e.g., PD-1 antibody combined with TIM-3 antibody, PD-1/TIM-3 bispecific antibodies).
Any other condition (including severe medical or psychiatric illness) or clinically significant laboratory abnormality that may affect patient safety or study integrity per investigator judgment.
(Applicable only to containing-LB4330 cohorts): History of Grade IV thrombocytopenia (per CTCAE) from any prior anti-cancer regimen within the past 2 years, or prior exposure to any interleukin-10 (IL-10) based agent.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yan Luan, Doctor | Contact | 86-21-54152522 | luanyn2@lnlbio.com | |
| Xiaohua Wu, Doctor | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Xiaohua Wu, Doctor | Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Shanghai | China |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C531958 | lenvatinib |
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| LB4330 | Biological | LB4330 (IV, Q2W for 4 cycles) |
|
| Lenvatinib | Drug | lenvatinib (oral, once daily for up to 2 years) |
|
defined as the time from the first documented response (CR or PR) to the first documented disease progression or death due to underlying cancer per RECIST 1.1. |
| Approximately 24 months |
| Disease Control Rate (DCR) | defined as the percentage of evaluable patients achieving a best overall response of complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1 assessed by both the investigator and an Independent Radiology Review Committee (IRRC). | Approximately 24 months |
| Progression-Free Survival (PFS) | defined as the time from the first dose to the first documented disease progression per RECIST 1.1 or death due to any cause (whichever occurred first) assessed by both the investigator and an IRRC. | Approximately 24 months |
| Overall Survival (OS) | Overall Survival is defined as the time from the date of first study treatment to the date of death from any cause or the date of censoring. | Until participant death/end of study,approximately 24 months |
| Safety and tolerability (Adverse Event reported per NCI-CTCAE v5.0) | Incidence of treatment-emergent adverse events (TEAEs) and treatment-related adverse events reported per NCI-CTCAE v5.0 | From the first dose administration to 30 days after the last dose |
| ADA Antibody Positivity Rate of LB1410 | ADA Antibody Positivity Rate of LB1410 | From the first dose administration to 30 days after the last dose |
| Pharmacokinetic (PK) parameters of LB1410-Maximum (peak) Plasma Concentration(Cmax) | The highest concentration a drug reaches in the bloodstream after a single dose. | From the first dose administration to Cycle 16 Day 1 (each cycle is 28 days) |
| Pharmacokinetic (PK) parameters of LB1410-Trough Concentration(Ctrough) | The minimum drug concentration at steady state, measured just before the next dose is administered. | From the first dose administration to Cycle 16 Day 1 (each cycle is 28 days) |
| Pharmacokinetic (PK) parameters of LB1410-Area Under the Curve at Steady State(AUCss) | The total area under the plasma concentration-time curve over one dosing interval at steady state, representing total drug exposure. | From the first dose administration to Cycle 16 Day 1 (each cycle is 28 days) |
Correlation between PD-L1 expression and clinical efficacy endpoints (ORR, DCR, PFS, OS) as assessed by the investigator according to RECIST 1.1 criteria.
| Until end of study,approximately 24 months |
| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |