Locally Advanced Cervical Cancer
Conditions
Keywords
Locally advanced cervical cancer, Neoadjuvant therapy, Immunotherapy, Chemotherapy, Iparomlimab/Tuvonralimab
Brief summary
The goal of this clinical trial is to learn if Iparomlimab/Tuvonralimab combined with nab-paclitaxel and cisplatin as neoadjuvant treatment can treat locally advanced cervical cancer in adult female patients. It will also learn about the safety of this combination regimen. The main questions it aims to answer are: What is the pathological complete response (pCR) rate after neoadjuvant combination therapy? What are the objective response rate, progression-free survival, overall survival, biomarker changes and tumor immune microenvironment changes in participants receiving this regimen? There is no comparison group in this single-arm study. Participants will: * Receive neoadjuvant treatment with Iparomlimab/Tuvonralimab, albumin-bound paclitaxel and cisplatin * Undergo radical surgery after completion of neoadjuvant therapy * Receive scheduled imaging, blood and tissue biomarker tests * Be followed up regularly for survival and safety assessment.
Interventions
BIOLOGICALIparomlimab/Tuvonralimab
5 mg/kg, intravenous infusion on Day 1 of each 3-week cycle, for a total of 3 cycles. It is a bispecific antibody targeting PD-1 and CTLA-4.
DRUGnab-paclitaxel
260 mg/m², intravenous infusion over 30 minutes on Day 1 of each 3-week cycle, for total 3 cycles.
DRUGCisplatin
75 mg/m², intravenous infusion on Day 1 of each 3-week cycle, for total 3 cycles.
AUC 5, intravenous infusion on Day 1 of each 3-week cycle, used as substitute for patients with cisplatin intolerance.
Sponsors
Xijing Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, non-randomized, open-label trial. All enrolled patients receive the same neoadjuvant combination regimen.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female patients aged between 18 and 70 years (inclusive); 2. Histologically confirmed cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma; 3. Previously untreated IB3 or IIA2 stage cervical cancer according to the FIGO 2018 staging system; 4. At least one measurable lesion based on RECIST version 1.1 criteria, with MRI-confirmed lymph node diameter less than 1.5 cm; 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 6.Patients must provide tumor tissue samples for PD-L1 expression testing, either formalin-fixed paraffin-embedded (FFPE) or fresh tumor tissue; 7\. Laboratory test requirements: 1. Hematology (no blood transfusion, hematopoietic growth factors, or other medications affecting blood counts within 14 days): absolute neutrophil count (ANC) \>= 1.5×10⁹/L; platelet count (PLT) \>= 80×10⁹/L; hemoglobin (HGB) \>= 90 g/L; 2. Biochemistry: serum creatinine \<= 1.5 × upper limit of normal (ULN), or creatinine clearance \>= 60 mL/min calculated using the Cockcroft-Gault formula if \>1.5 × ULN; total bilirubin (TBIL) \<= 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within acceptable range. 8\. Female subjects of childbearing potential must have a negative pregnancy test, not be breastfeeding, and must agree to use effective medical contraception from the time of informed consent signing until six months after the last study drug administration; 9. Subjects must voluntarily participate in the study, demonstrate good compliance with planned treatment and follow-up procedures, and be able to understand the study process and willingly sign the informed consent form
Exclusion criteria
1.Presence of distant metastatic disease; 2.Prior receipt of any anti-cancer therapy, including but not limited to surgery (excluding biopsy), radiation therapy, or systemic treatments such as chemotherapy, immunotherapy, or targeted therapy; 3. Previous treatment with immune checkpoint inhibitors, including but not limited to other anti-PD-1 or anti-PD-L1 antibodies; 4.Active malignancy within three years prior to first dosing, except for cervical cancer under investigation in this trial or any localized, curable tumors that have received definitive treatment (e.g., completely resected basal cell or squamous cell skin cancer, superficial bladder cancer, or cured in situ cancers such as breast carcinoma in situ); 5.Active autoimmune disease, or history of autoimmune disease within two years before enrollment requiring ongoing systemic treatment. Autoimmune diseases include but are not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, or asthma requiring bronchodilator intervention. However, participants with well-controlled type I diabetes, hypothyroidism managed solely with hormone replacement therapy, non-systemically treated skin conditions (such as vitiligo, psoriasis, or alopecia), or those whose condition is unlikely to recur without external triggers may still be considered for enrollment; 6.Primary immunodeficiency disorder or relevant medical history; 7.Received immunosuppressive agents (e.g., cyclosporine) within 14 days prior to enrollment or require daily systemic corticosteroid use (e.g., \>20 mg/day prednisone or equivalent), except for nasal sprays, inhalers, or other forms of localized steroid therapy; 8.Positive for human immunodeficiency virus antibody (HIV-Ab) or active syphilis infection; positive for hepatitis B surface antigen (HBsAg) with a viral load (HBV-DNA) \>500 IU/mL or \>2500 (units unclear, likely IU/mL.Viral load of hepatitis C virus (HCV-RNA) above the upper limit of normal for the testing facility. (Note: For participants who are positive for hepatitis B surface antigen \[HBsAg\], it is recommended to start antiviral therapy before the first administration of study drugs, using nucleoside analogs such as entecavir or tenofovir disoproxil fumarate.) 9. Active bacterial, fungal, or viral infection within 14 days prior to enrollment requiring intravenous antimicrobial, antifungal, or antiviral treatment. Participants receiving prophylactic anti-infective treatment without clinical signs of active infection at the time of screening may still be considered for inclusion; 10. Active tuberculosis or a history of tuberculosis; 11. History of severe cardiovascular disease within the past six months prior to enrollment, including but not limited to: stable angina classified as III-IV functional class; unstable angina or myocardial infarction; congestive heart failure classified as NYHA III-IV; clinically significant arrhythmias requiring medication (asymptomatic atrial fibrillation patients may be included if ventricular rate is well controlled); serious arterial/venous thromboembolic events such as hemorrhagic stroke, ischemic stroke, deep vein thrombosis, or pulmonary embolism; 12. Uncontrolled hypertension; 13. Interstitial lung disease or a history thereof, or non-infectious pneumonia requiring corticosteroid treatment; 14. Clinically significant hydronephrosis that, in the investigator's judgment, cannot be relieved through nephrostomy or ureteral stent placement; 15. Receipt of or planned administration of live or attenuated vaccines within 28 days before enrollment or during the study period; 16. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation; 17. History of severe allergic reactions to any component of monoclonal antibody formulations, or uncontrolled allergic asthma; 18. Contraindication to or history of severe allergic reaction to nab-paclitaxel, cisplatin, carboplatin, or any ingredient in the immunotherapy agents; 19. Participation in another clinical trial with administration of investigational drug within 28 days prior to enrollment; 20. Clear history of neurological or psychiatric disorders, substance abuse, or drug addiction that cannot be ceased or for which there is documented illicit drug use; 21. Any other condition deemed unsuitable for participation in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response (pCR) rate | Within 2 weeks after definitive radical surgery | The proportion of participants with pathological complete response (pCR), defined as no residual invasive carcinoma in the cervix and pelvic lymph nodes, evaluated by postoperative surgical pathology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | After completion of 3 cycles of neoadjuvant therapy | The proportion of participants whose Best Overall Response (BOR) is Complete Response (CR) or Partial Response (PR) as assessed according to RECIST version 1.1. |
| Progression-free survival (PFS) | Up to 36 months after radical surgery | Defined as the time from treatment initiation to any event, including disease progression, recurrence, or death from any cause. |
| Overall survival (OS) | Up to 36 months after radical surgery | Defined as the time from treatment initiation to death from any cause. |
| Treatment-related Adverse Events and Laboratory Abnormalities | From first study treatment administration to 30 days after the last dose of study drugs | Adverse events (AEs) and laboratory abnormalities, including category, incidence, grade (assessed per NCI-CTCAE v5.0), duration, and relationship to study treatment and immunotherapy. |
| Monitoring of immunological biomarkers related to treatment response | baseline, pre-surgery,and immediately after the surgery | Evaluation of tumor immune microenvironment biomarkers, including the quantity of tumor-infiltrating lymphocytes (TILs), the proportion of cytotoxic T cells (CD3+CD8+/CD3+), the proportion of regulatory T cells (Treg, CD3+FoxP3+CD8-/CD3+), the count of effector Treg cells (CD3+CD45RO+FoxP3+CD8-), the quantity of tumor-associated macrophages (TAM), and tertiary lymphoid structures. |
Countries
China
Contacts
CONTACTShujuan Liu, MD
CONTACTXiaohui Lv, MD
PRINCIPAL_INVESTIGATORShujuan Liu, MD
The First Affiliated Hospital of Airforce Medical University
Outcome results
None listed