RecruitingPhase 2NCT06878222

Iparomlimab and Tuvonralimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy for CC

Iparomlimab and Tuvonralimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy for Cervical Cancer: a Phase 2 Umbrella Trial


Sponsor

Obstetrics & Gynecology Hospital of Fudan University

Enrollment

35 participants

Start Date

Mar 15, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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

Sex: FEMALEMin Age: 18 YearsMax Age: 75 Years

Plain Language Summary

Simplified for easier understanding

This study tests a combination of two immunotherapy drugs — iparomlimab and tuvonralimab — together with standard chemotherapy (paclitaxel and cisplatin) as a treatment given before surgery for cervical cancer. The goal is to shrink the tumor as much as possible before surgery or to improve outcomes for locally advanced cases treated with radiation. **You may be eligible if:** - You have been confirmed by biopsy to have cervical squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma - You have locally advanced cervical cancer (FIGO 2018 stages IB3, IIA2, IIB, or IIICr) planning to have surgery, or stage IB1–IIB planning to have chemoradiation - You are between 18 and 70 years old - You have adequate kidney, liver, and bone marrow function - You have not received prior systemic treatment for cervical cancer **You may NOT be eligible if:** - You have already received chemotherapy, radiation, or immunotherapy for cervical cancer - You are pregnant or breastfeeding - You have a serious autoimmune disease or other condition that would make immunotherapy unsafe - You have distant metastases (cancer that has spread beyond the pelvis) Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGNeoadjuvant Chemotherapy

paclitaxel, 135-175mg/m2, q3w, 3 cycles

DRUGNeoadjuvant Chemotherapy

cisplatin, 75-80mg/m2, q3w, 3 cycles

DRUGImmunotherapy

Iparomlimab and Tuvonralimab, 5mg/kg, q3w, 3cycles

PROCEDURERadical surgery

After 3 cycles of neoadjuvant therapy, patients who achieved CR/PR will undergo radical hysterectomy plus lymphadenectomy

PROCEDUREFertility-preserving surgery

After 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.


Locations(1)

The Obstetrics & Gynecology Hospital of Fudan University

Shanghai, China

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NCT06878222


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