Efficacy and Safety of LB1410 Plus Lenvatinib With or Without LB4330 in Advanced Recurrent/Metastatic Cervical Cancer

A Multicenter, Randomized, Open-Label Phase II/III Clinical Study on the Efficacy and Safety of LB1410 Plus Lenvatinib With or Without LB4330 Versus Investigator's Choice of Chemotherapy in Advanced Recurrent/Metastatic Cervical Cancer

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.

Inclusion Criteria

1. Histologically confirmed cervical squamous cell carcinoma, adenosquamous carcinoma, or HPV-associated cervical adenocarcinoma.
2. Recurrent or metastatic cervical cancer with disease progression or intolerable toxicity after standard therapy, with no more than three prior lines of systemic therapy in the recurrent or metastatic setting, with only one prior line of therapy containing anti-PD-1/anti-PD-L1 agents.
3. At least one measurable lesion per RECIST v1.1 at screening period.
4. Age ≥18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Investigator-assessed life expectancy ≥12 weeks.
7. Adequate hematological function, liver function, renal function and coagulation function.
8. Adequately controlled blood pressure (BP) with or without antihypertensive medication.
9. Any related toxicity or prior adverse events (AEs) had recovered to baseline or ≤Grade 1 per NCI CTCAE v5.0.
10. Women of childbearing potential must agree to use effective contraception from the time of signing the informed consent form, throughout the study, and for 6 months after the last dose of study treatment.
11. The patient is capable of understanding and voluntarily signing the informed consent form.

Exclusion Criteria

1. For cohorts containing lenvatinib, patients meeting any of the following criteria are ineligible:

   1. Radiographic (CT or MRI) evidence of tumor invasion around major blood vessels, or investigator judgment that the tumor is highly likely to invade major blood vessels during the study, leading to life-threatening hemorrhage;
   2. History of bleeding, coagulation disorders, or current use of warfarin, aspirin, or other antiplatelet agents;
   3. Urine protein ≥2+ and 24-hour urine protein quantification ≥1.0 g;
   4. Factors affecting oral drug absorption;
   5. Intestinal metastases or existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistulas;
   6. History of hypertensive crisis or hypertensive encephalopathy.

2. Pregnant or breastfeeding women.

3. History of ≥Grade 3 immune-related adverse events (irAEs) during prior immunotherapy.

4. Active autoimmune disease or symptomatic autoimmune disease.

5. Any of the following prior treatments:

   1. Live or attenuated live vaccines within 4 weeks before the first dose;
   2. Immunomodulatory drugs (e.g., thymosin, interleukin-2, interferon) within 14 days before the first dose;
   3. History of allogeneic organ transplantation, allogeneic peripheral hematopoietic stem cell transplantation, or bone marrow transplantation.

6. Positive HIV test, active syphilis, active hepatitis B virus (HBV) infection, or active hepatitis C virus (HCV) infection.

7. Other malignancies within the past 3 year.

8. Leptomeningeal metastasis, spinal cord compression, symptomatic or unstable brain metastases.

9. Uncontrolled or poorly controlled diabetes.

10. Arterial/venous thrombotic events within 6 months.

11. Clinically significant and unstable pleural, peritoneal, or pericardial effusion.

12. Known interstitial lung disease.

13. 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).

14. 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.

15. (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.