A Clinical Study to Explore the Efficacy and Safety of Tislelizumab in Combination With Bevacizumab and Chemotherapy in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

Last updated: July 12, 2022
Sponsor: Zhejiang Cancer Hospital
Overall Status: Active - Recruiting

Phase

2

Condition

Cervical Cancer

Vaginal Cancer

Pelvic Cancer

Treatment

N/A

Clinical Study ID

NCT05247619
BGB-A317-2007
  • Ages > 18
  • Female

Study Summary

Efficacy and safety of Tislelizumab combined with Bevacizumab and chemotherapy in patients with persistent, recurrent or metastatic cervical cancer.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Voluntary participation and signature of informed consent;
  2. Age ≥18;
  3. Eastern United States Cancer Collaboration Group (ECOG) score 0-1;
  4. Patients with metastatic (IVB), persistent or first recurrent cervical cancer isunsuitable for surgical treatment;
  5. Histopathology was defined as: cervical squamous cell carcinoma, adenocarcinoma,adenosquamous carcinoma, patients included in adenocarcinoma histology will be limitedto 20% of the entire study population;
  6. Patients must have lesions that can be measured according to RECIST v1.1 criteria;
  7. The main organs function well and are defined as:
  • Patients received no blood, platelet transfusion or growth factor supporttreatment within 14 days ≤ the beginning of treatment and was required to:
  • x 109/L ANC ≥1.5
  • Platelet ≥100 x 109/L
  • g/L ≥90
  • AST and ALT≤2.5 times ULN (5 times if liver metastasis occurs)
  • Serum total bilirubin ≤ ULN 1.5 times
  • Serum creatinine <1.5x upper limit (ULN)
  • Urine routine examination, urine protein <2+
  • The internationally standardized ratio (INR)≤1.5 or prothrombin time ULN 1.5times
  • The activated partial thromboplastin time (aPTT)≤1.5 times ULN time
  • Serum albumin ≥30 g/L
  1. Life expectancy ≥3 months;
  2. Pregnant women must agree to effective contraception ≥120 days during the study periodand after the last drug administration, and the results of serum pregnancy tests werenegative 7 days ≤ before the first drug administration;

Exclusion

Exclusion Criteria:

  1. Patients whose bilateral hydronephrosis can not be alleviated by ureteral stent orpercutaneous drainage; non-communicable cystitis CTCAE(5.0 Edition)≥ grade 2;
  2. Exclusion criteria of bevacizumab, i.e. clinical significance of cardiovascular andcerebrovascular diseases, abdominal fistula or gastrointestinal perforation history,acute intestinal obstruction or subimpedance, active bleeding;
  3. hypertension (systolic blood pressure greater than 140 mmHg and/or diastolic bloodpressure greater than 90 mmHg), hypertension crisis or history of hypertensiveencephalopathy, which remains uncontrolled under medication;
  4. Previous medical history showing newly discovered thrombotic disease within 6 monthsof screening or during screening; patients with severe wound nonunion, ulcers orfractures;
  5. Patients with other malignancies and brain metastases;
  6. Patients with central nervous system diseases, including uncontrolled seizure standarddrug therapy, or historical cerebrovascular accidents (CVA, stroke), transientischemic attacks (TIA) or subarachnoid hemorrhage within six months.
  7. Previous treatment with antiprogrammed cell death protein-1(anti PD-1), antiprogrammeddeath ligand-1(anti PD-L1) or anti PD-L2 drugs, or have received another drugtreatment (e.g., cytotoxic T lymphocyte-associated antigen-4[ CTLA-4]、OX-40,] antigenpatients CD137[ tumor necrosis factor receptor superfamily member 9(TNFRSF9)]; Apatient who has previously received any VEGF drugs, including bevacizumab.
  8. Patients who received live vaccinations or had undergone major surgery within 30 daysprior to the first administration of the study; patients who were expected to undergoinvasive surgery during treatment;
  9. Active autoimmune diseases requiring systemic treatment in the past two years;
  10. ≤14 days before the first administration of the study drug, any condition requiringsystemic treatment with corticosteroids (prednisone or equivalent >10 mg/ days) orother immunosuppressive drugs;
  11. History of known human immunodeficiency virus (HIV) infection;
  12. Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA >500 IU/mL) or active HCV carriers with detectable levels; Note: Non-active hepatitisB surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA <500 IU/mL) can be enrolled;
  13. History of interstitial lung disease, non-infectious pneumonia or uncontrolleddisease, including pulmonary fibrosis, acute lung disease, etc;
  14. Severe chronic or active infections (including tuberculosis infections) requiringsystemic antimicrobial, antifungal or antiviral therapy within 14 days prior to thefirst administration of the study drug Note: Patients with viral hepatitis are allowedantiviral therapy;
  15. with severe cardiovascular diseases such as myocardial infarction, acute coronarysyndrome, or coronary angioplasty/stenting/bypass transplantation in the past 6months, or new york heart disease association (NYHA) class ii-class IV congestiveheart failure (CHF), or history of class NYHA III or IV CHF;
  16. who are known to be allergic to components of a study drug or its analog;
  17. Participate in another clinical study at the same time, unless it is an observational (non-intervention) clinical study or at a follow-up period of an intervention study;
  18. Pregnant or lactating women;
  19. Previous heterogenous stem cell transplantation or organ transplantation;
  20. Other conditions judged by the researchers did not meet the requirements of the group.

Study Design

Total Participants: 49
Study Start date:
June 30, 2022
Estimated Completion Date:
January 31, 2025

Study Description

The current standard treatment for persistent, metastatic and recurrent cervical cancer is platinum-based combination chemotherapy as its first-line treatment option. However, the current treatment plan still can not meet the clinical needs of cervical cancer treatment, most patients will progress about 6 months after first-line treatment.

At present, there are many clinical research evidence to support the PD-1 antibody for the treatment of recurrent cervical cancer. Immunotherapy can restore the environment of immune support and promote vascular normalization, while anti-angiogenesis can not only normalize tumor vessels, but also block immunosuppressive signals through many ways, so the two mechanisms complement each other. Inhibition of these two pathways will bring better and more lasting clinical benefits to cervical cancer patients.

This study explores the efficacy and safety of tirelizumab combined with bevacizumab and chemotherapy in patients with persistent, recurrent, or metastatic cervical cancer. combining with immune checkpoint inhibitors on the basis of standard treatment regimens has a more potent and durable antitumor ability mechanistically, no significant adverse reactions overlap between immunotherapy and existing standard regimens from a safety perspective, and multiple immune checkpoint combined with antiangiogenic studies confirm safety in cervical cancer.

Connect with a study center

  • Zhejiang Cancer Hospital

    Hangzhou, Zhejiang
    China

    Active - Recruiting

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