QL1706 Plus Neoadjuvant Chemotherapy Followed by Type I Hysterectomy for Locally Advanced Cervical Cancer

Iparomlimab and Tuvonralimab (QL1706) Combined With Neoadjuvant Chemotherapy Followed by Type I Hysterectomy for Locally Advanced Cervical Cancer（QNACTH）: A Prospective, Single-Arm, Multicenter, Phase 2 Trial

The goal of this clinical trial is to determine the effectiveness of the combination therapy of Eparbrutinib (QL1706) with neoadjuvant chemotherapy followed by Type I hysterectomy in treating locally advanced cervical cancer. Additionally, it will assess the safety profile of this treatment regimen. The main questions it aims to answer are:

1. Does the combination of Eparbrutinib (QL1706) with neoadjuvant chemotherapy lead to a higher rate of complete pathological response (pCR) compared to chemotherapy alone?
2. What are the medical complications and side effects experienced by participants during the treatment with Eparbrutinib (QL1706)?

Researchers will compare the outcomes of patients receiving Eparbrutinib (QL1706) combined with neoadjuvant chemotherapy to those receiving standard treatment to evaluate the effectiveness in treating locally advanced cervical cancer.

Participants will:

1. Take Eparbrutinib (QL1706) alongside cisplatin and albumin-bound paclitaxel every three weeks for three cycles.
2. If the lesion was reduced to less than or equal to 2cm, conectomy was performed; if the pathological results indicated no high-risk factors, total hysterectomy was performed, and QL1706+TC was treated after surgery. If the lesion is larger than 2cm, a type III hysterectomy is performed and adjuvant treatment is determined according to sedlis criteria after surgery.
3. Visit the clinic regularly for checkups, tests, and assessments throughout the treatment period.
4. Keep a diary of their symptoms, side effects, and any changes in their health status.

This study is designed to provide insights into the potential benefits of adding Eparbrutinib (QL1706) to the standard neoadjuvant chemotherapy regimen for locally advanced cervical cancer, which may lead to improved treatment outcomes and survival rates for patients.

Inclusion Criteria:

1. Clinically diagnosed with untreated cervical cancer at stages IB3, IIA2, and resectable IIIC1r (according to the FIGO standards of 2018; determined by two senior physicians or above through gynecological examination and imaging studies);
2. At baseline, there is at least one measurable tumor lesion according to the RECIST 1.1 criteria, with the size of the lesion primarily determined by magnetic resonance imaging;
3. Pathologically confirmed cervical cancer, including squamous cell carcinoma (all grades), common type adenocarcinoma (Silva classification types A or B, or differentiated grades G1 or G2), and adenosquamous carcinoma (differentiated grades G1 or G2);
4. Patients must be aged between 18 and 70 years inclusive;
5. ECOG performance status score of 0 or 1;
6. Laboratory tests: White blood cell count (WBC) ≥ 3.5 × 10^9/L, neutrophil count (NEU) ≥ 1.5 × 10^9/L, platelet count (PLT) ≥ 100 × 10^9/L, serum bilirubin ≤ 1.5 times the upper limit of normal, transaminases ≤ 1.5 times the upper limit of normal, blood urea nitrogen (BUN) and creatinine (Cr) within normal limits;
7. Capable of follow-up and good compliance;
8. Able to sign an informed consent form, including adherence to the requirements and restrictions listed in the informed consent and this protocol.

Exclusion Criteria:

1. Participants with active, known, or suspected autoimmune diseases, or a history of autoimmune diseases, except for the following conditions: vitiligo, alopecia, Graves' disease, psoriasis, or eczema that does not require systemic treatment within the last 2 years, asymptomatic hypothyroidism or requiring only a stable dose of hormone replacement therapy (due to autoimmune thyroiditis), type 1 diabetes requiring only a stable dose of insulin replacement therapy, asthma that has completely resolved in childhood and does not require intervention in adulthood, or diseases that do not relapse without external triggers;
2. Previously treated with immune checkpoint inhibitors, including but not limited to other anti-PD-1, anti-PD-L1 antibodies, CTLA-4 antibodies, or any treatments targeting immune co-stimulatory factors (such as antibodies targeting ICOS, CD40, CD137, GITR, OX40, etc.) or other mechanisms of tumor immunotherapy;
3. Known allergic reactions to any components and/or excipients of the investigational medication;
4. Received immunosuppressive drugs or systemic corticosteroids for immunosuppression within 2 weeks prior to the study medication (more than 10mg/day of prednisone or other equivalent drugs), with the exception of local, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids;
5. Received traditional Chinese medicine with antitumor effects or drugs with immunomodulatory effects (such as thymic peptides, interferons, interleukin-2) within 2 weeks prior to the study;
6. Active systemic infections requiring systemic treatment;
7. Experienced severe infections within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia;
8. Untreated chronic hepatitis B patients, or hepatitis B virus (HBV) carriers with HBV DNA greater than 1000 IU/mL, or patients with active hepatitis C. Non-active HBsAg carriers, treated and stable hepatitis B patients (HBV DNA < 1000 IU/mL), and cured hepatitis C patients are eligible. Subjects with positive HCV antibodies are only eligible if HCV RNA testing is negative;
9. Known active pulmonary tuberculosis (TB), suspected active TB patients should undergo chest X-ray and sputum tests, combined with clinical symptoms and signs to rule out;
10. Immunodeficiency or human immunodeficiency virus (HIV antibody positive);
11. Participants with active inflammatory bowel disease or a history of such diseases (such as Crohn's disease, ulcerative colitis, or chronic diarrhea). Participants who cannot swallow or have malabsorption syndrome, uncontrolled nausea, vomiting, diarrhea, or other gastrointestinal diseases that severely affect drug intake and absorption;
12. Known interstitial lung disease, symptomatic or likely to hinder the detection or treatment of immune-related pneumonia;
13. Received live vaccines or attenuated vaccines within 4 weeks prior to the first trial dose, with the exception of inactivated seasonal influenza vaccines;
14. Patients who have undergone allogeneic bone marrow transplantation or solid organ transplantation;
15. History of primary malignant tumors within the last 5 years;
16. Participants who have undergone major surgery (such as laparotomy, thoracotomy, organ resection, etc.) and severe trauma within 28 days prior to the first dose, with the exception of implantable infusion devices;
17. History of gastrointestinal perforation, gastrointestinal fistula, or female genital fistula;
18. Uncontrolled other comorbidities, symptoms, or medical history, including: ① Those with one of the following cardiovascular or cerebrovascular diseases or risk factors: myocardial infarction, unstable angina, pulmonary embolism, acute/persistent myocardial ischemia, cerebrovascular accident, transient ischemic attack, or other clinically significant/requiring medication intervention arterial venous thrombosis, embolism, or cerebral ischemic events; symptoms of congestive heart failure within 6 months (New York Heart Association (NYHA) class III or above); ② History of clinically significant bleeding symptoms or obvious bleeding features within 1 month prior to the first dose, such as gastrointestinal bleeding, peptic ulcer bleeding, or vasculitis; ③ Clinical manifestations of active hemoptysis, active diverticulitis, abdominal abscess, and gastrointestinal obstruction; ④ Those with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; ⑤ History of liver or kidney abnormalities or surgery;
19. Pregnant or nursing women; women of childbearing age who refuse to accept contraceptive measures during neoadjuvant immunotherapy;
20. Simultaneously participating in other interventional clinical trials, participation in observational and non-interventional clinical trials is allowed;
21. Any condition deemed by the investigator to pose a risk when receiving the study medication, or that would interfere with the safety evaluation of the study medication or the interpretation of the study results.