Neoadjuvant Iparomlimab and Tuvonralimab Plus Chemotherapy-eclipse for Locally Advanced Cervical Cancer (NICE-CC)

Neoadjuvant Therapy of Iparomlimab and Tuvonralimab Combined With Chemotherapy-eclipse for Locally Advanced Cervical Cancer：A Single-arm, Open-label, Phase II Trial

Locally advanced cervical cancer (LACC) remains a significant global health concern with limited treatment options. Recent advancements suggest that using neoadjuvant anti-PD-1 inhibitors in combination with chemotherapy, followed by radical surgery, may be an effective treatment strategy for patients with PD-L1-positive LACC. This study aims to evaluate the efficacy and safety of preoperative treatment with iparomlimab and tuvonralimab-a bifunctional PD-1/CTLA-4 dual blocker-combined with chemotherapy for LACC.

A total of 43 patients with FIGO 2018 stages IB3, IIA2, IIB, or IIIC1r will receive a combination treatment consisting of iparomlimab and tuvonralimab (5 mg/kg administered intravenously), cisplatin (75-80 mg/m², intravenously), and nab-paclitaxel (260 mg/m², intravenously) for one cycle. Following this, patients will receive two additional cycles of iparomlimab and tuvonralimab at the same dosage of 5 mg/kg, administered at three-week intervals. After completing three cycles of neoadjuvant treatment, patients who show a complete response (CR) or partial response (PR) will undergo radical surgery. The decision regarding subsequent adjuvant therapy will be guided by the NCCN guidelines. In contrast, patients with stable or progressive disease will proceed to concurrent chemoradiotherapy (CCRT).

Inclusion Criteria:

• 1、Written informed consent
• 2、18-70 years old
• 3、Adequate organ function and ECOG of 0 ~1
• 4、Without systemic therapy at the time of enrollment
• 5、FIGO 2018 stage IB3, IIA2, or IIIC1r
• 6、Histologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
• 7、Measurable lesions could be defined by RECIST v1.1
• 8、Willing to get blood/ tumor tissue tested
• 9、Patients who observed the rules about the scheduled visit, study schedule, and medical examination
• 10、The function of major organs is normal, and the following criteria are met:
• 10.1 Blood routine examination must meet: (no blood transfusion within 14 days)

Hb≥90g/L:

ANC≥1.5x10^9/L; PLT≥100x10^9/L;

• 10.2 The biochemical examination must meet the following standards BIL < 1.5 × ULN; ALT and AST < 2.5xULN; ALB≥ 28 g/L
• 11、Patients who are willing and able to comply with visiting arrangements, treatment plans, laboratory tests, and other research procedures.

Exclusion Criteria:

• 1、History of other malignancies within 3 years
• 2、Participate in other clinical trials at the same time
• 3、Active autoimmune disease, which needs systemic therapy
• 4、Uncontrolled infection, which needs systemic therapy
• 5、History of allogeneic tissue/solid organ transplant
• 6、Serious illness, such as severe mental disorders, cardiac disease, coagulation disorders, digestive system disease, etc
• 7、Active HBV, HCV, or HIV infection
• 8、Pregnant or lactating female patients
• 9、Drug or alcohol abuse
• 10、 Unable or unwilling to sign the informed consent