About this trial
Currently, the survival rate of locally advanced cervical cancer is low, posing a significant challenge in the treatment of cervical cancer. Radical chemoradiotherapy is considered the standard treatment for patients with locally advanced cervical cancer. However, 23.3% to 34.4% of patients still experience recurrence or subsequent metastasis. Radical surgery following neoadjuvant chemotherapy is an alternative to concurrent chemoradiotherapy, but it also has limitations: for approximately 9.8% to 30.6% of patients who do not respond to neoadjuvant chemotherapy, effective local treatment may be delayed. Additionally, more than 30% of patients still require adjuvant radiotherapy or chemoradiotherapy after surgery, significantly increasing the risk of complications. Therefore, there is an urgent need to explore alternative or improved treatment methods for neoadjuvant chemotherapy in locally advanced cervical cancer.
An increasing number of women are being diagnosed with cervical cancer during their childbearing years, many of whom have a desire to preserve their fertility. For selected patients with stage IB2 cervical cancer, options include abdominal radical trachelectomy or radical trachelectomy following neoadjuvant chemotherapy. However, compared to conservative surgeries such as conization or partial cervical resection, radical trachelectomy is associated with less favorable fertility rates and pregnancy outcomes, with significantly higher rates of infertility, miscarriage, and preterm birth. For patients with stage IB3 or IIA1-IIA2 cervical cancer, the current standard surgical approach is radical hysterectomy, which does not preserve fertility. Current research suggests that neoadjuvant chemotherapy can shrink tumor size, decrease lymph node and distant metastases, and reduce the need for postoperative adjuvant radiotherapy. This offers hope for young cervical cancer patients who wish to preserve fertility, as it may reduce tumor size, thereby allowing for less extensive fertility-sparing surgery, improving pregnancy outcomes, or even making fertility-sparing surgery a viable option.
In recent years, immunotherapy has gradually become a research hotspot in cancer treatment. Anti-PD-1/PD-L1 monoclonal antibodies, as a type of immunotherapy drug, have demonstrated promising anti-tumor efficacy and low side effects in clinical trials. Iparomlimab and Tuvonralimab is a novel therapeutic biological product targeting both PD-1 and CTLA-4. It is composed of two engineered monoclonal antibodies (anti-PD-1 and anti-CTLA-4) expressed in a fixed ratio and has shown significant efficacy in cervical cancer patients. Therefore, given the urgent need to improve neoadjuvant therapy for locally advanced cervical cancer and fertility-preserving neoadjuvant therapy for early-stage cervical cancer patients, this study is being conducted to explore and evaluate the efficacy and safety of Iparomlimab and Tuvonralimab combined with paclitaxel and cisplatin as neoadjuvant therapy for cervical cancer. Additionally, the study aims to investigate the relationship between tumor-related biomarkers and the risk of recurrence.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma.
-Arm 1 (Locally Advanced cervical cancer): Patients with locally advanced cervical cancer classified as FIGO 2018 stages IB3, IIA2, IIB, or IIICr (lesion ≥4 cm, confirmed by MRI).
Arm2 (cervical cancer patients desiring fertility-sparing treatment): Patients with cervical cancer classified as FIGO 2018 stages IB2, IB3 (lesion ≤6 cm), IIA1, or IIA2 (lesion ≤6 cm) who have a strong desire to preserve fertility.
Arm2 (cervical cancer patients desiring fertility-sparing treatment): Age 18-45 years.
Disqualifiers
Histological subtypes or disease stages other than those permitted in inclusion criteria 1) and 2).
Severe hypersensitivity (≥ Grade 3) to cisplatin, paclitaxel, iparomlimab and tuvonralimab, and/or any of their excipients.
Participation in another clinical trial within 4 weeks prior to enrollment.
Administration of inactivated vaccines within 30 days before the first study treatment or planned vaccination during the study period.
Trial design
Single group
Treatments tested in this trial
Neoadjuvant Chemotherapy
Drugpaclitaxel, 135-175mg/m2, q3w, 3 cycles
Neoadjuvant Chemotherapy
Drugcisplatin, 75-80mg/m2, q3w, 3 cycles
Immunotherapy
DrugIparomlimab and Tuvonralimab, 5mg/kg, q3w, 3cycles
Radical surgery
Procedure/SurgeryAfter 3 cycles of neoadjuvant therapy, patients who achieved CR/PR will undergo radical hysterectomy plus lymphadenectomy
Fertility-preserving surgery
Procedure/SurgeryAfter 3 cycles of neoadjuvant therapy, patients who achieved CR/PR will undergo Fertility-preserving surgery. For stage IB1/IB2 patients, conization or simple trachelectomy plus lymphadenectomy will be performed. For stage IIA1/IIA2 patients, radical trachelectomy plus lymphadenectomy will be performed.
Treatment groups
Trial outcomes
Primary outcomes
Objective Response Rate (ORR)
ORR measures the proportion of patients whose cervical cancer shows a complete response (CR) or partial response (PR) to neoadjuvant therapy in this study. Complete Response (CR) means total disappearance of all detectable tumors and partial Response (PR) means significant reduction in tumor size larger than 30% according to RECIST guidelines.
Pathological Complete Response (pCR)
Pathological Complete Response (pCR) refers to the absence of detectable cancer cells in the tissue removed during surgery after neoadjuvant therapy which is examined under a microscope by a pathologist.
changes in tumor-related biomarkers
Secondary outcomes
OS (Overall Survival)
DFS (Disease Free Survival)
adverse events
Other outcomes
Pregnancy rate
infant survival rate
Sponsors and contacts
Click on the lead sponsor to view all of their trials.