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

NCT06878222 | Recruiting Phase 2

• 1 other identifier: QIBA-CER-003
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cervical Cancers

Keywords

cervical cancer; neoadjuvant therapy; Iparomlimab and Tuvonralimab; immunotherapy; fertility-preserving

Outcome Measures

Primary Outcomes (3)

• 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.

  9 weeks

• 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.

  3 months

• changes in tumor-related biomarkers

  3 months

Secondary Outcomes (3)

• OS (Overall Survival)

  2 years

• DFS (Disease Free Survival)

  2 years

• adverse events

  2 years

Other Outcomes (2)

• Pregnancy rate

  2 years

• infant survival rate

  3 years

Study Arms (2)

Arm1: locally advanced cervical cancer

ACTIVE COMPARATOR

Patients with locally advanced cervical cancer classified as FIGO 2018 stages IB3, IIA2, IIB, or IIICr (lesion ≥4 cm, confirmed by MRI); histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma；18-75 years old.

Drug: Neoadjuvant Chemotherapy; Drug: Immunotherapy; Procedure: Radical surgery

Arm2: cervical cancer patients desiring fertility-preserving treatment

ACTIVE COMPARATOR

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； histologically confirmed cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma； 18-45 years old.

Drug: Neoadjuvant Chemotherapy; Drug: Immunotherapy; Procedure: Fertility-preserving surgery

Interventions

Neoadjuvant Chemotherapy DRUG

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

Arm1: locally advanced cervical cancer; Arm2: cervical cancer patients desiring fertility-preserving treatment

Immunotherapy DRUG

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

Arm1: locally advanced cervical cancer; Arm2: cervical cancer patients desiring fertility-preserving treatment

Radical surgery PROCEDURE

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

Arm1: locally advanced cervical cancer

Fertility-preserving surgery PROCEDURE

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.

Arm2: cervical cancer patients desiring fertility-preserving treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ）Planned to undergo surgical treatments of cervical cancer.
• \) -Arm 1 (Locally Advanced cervical cancer): Age 18-75 years.
• Arm2 (cervical cancer patients desiring fertility-sparing treatment): Age 18-45 years.
• \) ECOG performance status score: 0-1. 6) No prior immunotherapy received by the participant. 7) Expected survival period ≥6 months. 8) Women of childbearing potential must agree to use contraception (e.g., intrauterine device, oral contraceptives, or condoms) during the study and for 6 months after the study ends. A negative serum or urine pregnancy test within 7 days before study enrollment is required, and the patient must not be breastfeeding.
• \) Adequate organ function as defined by the protocol, with test samples collected within 7 days before the start of study treatment.
• \) Participants voluntarily join the study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.

You may not qualify if:

• 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.
• Treatment with systemic immunostimulants, colony-stimulating factors, interferons, interleukins, or combination vaccines within 6 weeks or 5 half-lives (whichever is shorter) before the first dose.
• Diagnosis of immunodeficiency or chronic systemic steroid therapy (exceeding 10 mg prednisone equivalent per day) or any other form of immunosuppressive therapy within 7 days before the first dose.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within the past 2 years.
• History of (non-infectious) pneumonitis requiring steroid treatment or current (non-infectious) pneumonitis.
• Active infection requiring systemic treatment.
• Known history of HIV infection.
• Known history of hepatitis B (defined as HBsAg reactivity) or active hepatitis C virus infection (defined as detectable HCV RNA \[qualitative\]).
• Known history of active tuberculosis (TB; Mycobacterium tuberculosis).
• Prior allogeneic tissue/solid organ transplantation.
• Central nervous system metastases, such as brain metastases.
• Uncontrolled pleural or peritoneal effusion.
• Impaired mobility due to pathological fractures caused by bone metastases.

Sponsors & Collaborators

• Obstetrics & Gynecology Hospital of Fudan University: lead

Study Sites (1)

The Obstetrics & Gynecology Hospital of Fudan University

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Neoadjuvant Therapy; Immunotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Immunomodulation; Biological Therapy

Study Officials

• Keqin Hua, Doctor

  Gynecology and obstetrics hospital of fudan university

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junjun Qiu

CONTACT

18017738139; qiujunjun1113@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Gynecological Oncology

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 14, 2025
• Study Start: March 15, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2030
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)