Cervical CancersPhase 2NCT06878222
Iparomlimab and Tuvonralimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy for CC
A Phase 2 study testing Neoadjuvant Chemotherapy, Immunotherapy and Radical surgery in people with Cervical Cancers, run by Obstetrics & Gynecology Hospital of Fudan University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Cervical Cancers
- What is being tested?
- Neoadjuvant Chemotherapy, Immunotherapy and Radical surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2025to 31 Mar 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 3）Planned to undergo surgical treatments of cervical cancer.
- 4) -Arm 1 (Locally Advanced cervical cancer): Age 18-75 years.
- Arm2 (cervical cancer patients desiring fertility-sparing treatment): Age 18-45 years.
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- 5) 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.
- 9) Adequate organ function as defined by the protocol, with test samples collected within 7 days before the start of study treatment.
- 10) Participants voluntarily join the study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.
Who cannot join
- 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.
- 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.
Show all 22Show fewer
- 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.
- Insufficient bone marrow function (without transfusion within 14 days): a) Absolute neutrophil count (ANC) <1.5×10⁹/L;b) Platelets <100×10⁹/L; c) Hemoglobin <9 g/dL.
- Liver abnormalities: a) ALT, AST, or ALP >2.5× upper limit of normal (ULN) without liver metastasis or >5×ULN with liver metastasis; b) Total bilirubin >1.5×ULN (>3×ULN in patients with Gilbert's syndrome); c) Decompensated cirrhosis (Child-Pugh class B or C); d) HBsAg-positive with HBV DNA ≥2000 IU/mL (patients with HBsAg-positive and HBV DNA <2000 IU/mL must receive at least 2 weeks of anti-HBV therapy before the first dose); e) HCV antibody-positive with detectable HCV RNA.
- Kidney abnormalities: a) Serum creatinine >1.5×ULN or estimated creatinine clearance <60 mL/min using the Cockcroft-Gault formula; b) Urinalysis showing protein ≥++ and confirmed 24-hour urine protein >1.0 g; c) Renal failure requiring hemodialysis or peritoneal dialysis; d) History of nephrotic syndrome.
- Bleeding risk: a) Coagulation abnormalities: Activated partial hromboplastin time (APTT) or thrombin time (TT) >1.5×ULN, or international normalized ratio (INR) >1.5 (>2.5 for patients requiring anticoagulation therapy); b) History of bleeding (e.g., hemoptysis), coagulation disorders, or current use of warfarin, aspirin, low-molecular-weight heparin, or other antiplatelet agents (except for aspirin ≤100 mg/d for prophylaxis); c) Any signs or history of bleeding diathesis, regardless of severity; d) Active gastrointestinal bleeding, evidenced by hematemesis, hematochezia, or melena within the past 3 months, without resolution confirmed by endoscopy or colonoscopy; e) Any CTCAE ≥ Grade 3 bleeding or hemorrhagic event within 4 weeks before the first dose.
- Cardiovascular and cerebrovascular abnormalities: a) Any of the following within 12 months before the first dose: ≥ Grade 2 myocardial ischemia, yocardial infarction, arrhythmias, ≥ Grade 3 cardiac insufficiency, uncontrolled angina, coronary/peripheral artery bypass graft surgery, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack; b) Deep vein thrombosis or pulmonary embolism within 6 months before the first dose; c) Left ventricular ejection fraction (LVEF) <50% assessed by Doppler ultrasound; d) Average QTc interval corrected by Fridericia's formula (QTcF) (based on at least 3 consecutive ECG readings): ≥470 ms for females; e) Uncontrolled hypertension (at least 2 measurements showing systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
- Other factors judged by the investigator as potentially affecting study results or leading to premature termination, such as alcoholism, drug abuse, other severe diseases (including mental illness) requiring concurrent treatment, significant laboratory abnormalities, or family/social factors that may compromise patient safety.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Obstetrics & Gynecology Hospital of Fudan University
Shanghai
Junjun Qiu, +86-18017738139, qiujunjun1113@163.com
About this study
Official title: Iparomlimab and Tuvonralimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy for Cervical Cancer: a Phase 2 Umbrella 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.
Read the detailed description
In recent years, anti-PD-1/PD-L1 monoclonal antibodies, as a type of immunotherapy drug, have demonstrated promising anti-tumor efficacy in the treatment of cervical cancer patients. PD-1 (Programmed cell death protein 1) is a surface immune checkpoint protein that, by binding to its ligand PD-L1, inhibits the activation of T cells, thereby allowing tumor cells to evade immune system attacks. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, a phase II clinical study was reported on the use of immunotherapy (sintilimab) combined with paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer. The results showed that the primary endpoint, pathological complete response (pCR), was 32.6% (14/43), and the best response rate (residual tumor infiltration depth less than 3 mm) was 51.2% (22/43).
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 produced as a single product from a single cell line. It offers the following advantages:
- Dual immune targets of PD-1 and CTLA-4 monoclonal antibodies: The anti-PD-1 antibody relieves T cell killing inhibition, while the anti-CTLA-4 antibody relieves T cell activation inhibition, working synergistically to enhance efficacy.
- Optimal 2:1 ratio of anti-PD-1 to anti-CTLA-4 antibodies: A dosing regimen of 5 mg/kg every 3 weeks ensures effective blood concentration, balancing efficacy and safety.
- Flexible antibody subtype design: The anti-PD-1 antibody uses the IgG4 subtype, which lacks ADCC (antibody-dependent cellular cytotoxicity) effects and does not deplete effector T cells. The anti-CTLA-4 antibody uses the IgG1 subtype, which has ADCC effects and can eliminate regulatory T cells, further enhancing efficacy.
- R255K mutation in the anti-CTLA-4 antibody: This mutation reduces the affinity of the anti-CTLA-4 antibody for the neonatal Fc receptor (FcRn), shortening its half-life to 1 week and lowering its blood concentration, thereby improving safety while maintaining efficacy.
Currently, Iparomlimab and Tuvonralimab for recurrent or metastatic cervical cancer as a second-line or later treatment has shown an objective response rate (ORR) of 33.8% and a progression-free survival (PFS) of 5.4 months, with a favorable safety profile. When combined with chemotherapy as first-line treatment for recurrent or metastatic cervical cancer, the ORR was 75.9%, PFS was 15.1 months, and immune-related adverse events occurred in 16.7% of cases. These results indicate that Iparomlimab and Tuvonralimab, both as monotherapy and in combination therapy, demonstrates significant anti-tumor activity and safety, suggesting that dual-target antibodies are effective for advanced cancer patients.
Therefore, given the urgent need to improve neoadjuvant therapy for locally advanced cervical cancer and neoadjuvant fertility-preserving therapy for early-stage cervical cancer, 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 locally advanced cervical cancer and fertility-preserving neoadjuvant therapy for cervical cancer. Additionally, the study aims to investigate the relationship between tumor-related biomarkers and the risk of recurrence, potentially offering new insights for optimizing fertility-preserving and non-preserving neoadjuvant therapies for cervical cancer.
- Conditions
- Cervical Cancers
- Being tested
- Neoadjuvant Chemotherapy, Immunotherapy, Radical surgery, Fertility-preserving surgery
- Keywords
- cervical cancer, neoadjuvant therapy, Iparomlimab and Tuvonralimab, immunotherapy, fertility-preserving
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neoadjuvant ChemotherapyDrug
paclitaxel, 135-175mg/m2, q3w, 3 cycles
Neoadjuvant ChemotherapyDrug
cisplatin, 75-80mg/m2, q3w, 3 cycles
ImmunotherapyDrug
Iparomlimab and Tuvonralimab, 5mg/kg, q3w, 3cycles
Radical surgeryProcedure or surgery
After 3 cycles of neoadjuvant therapy, patients who achieved CR/PR will undergo radical hysterectomy plus lymphadenectomy
Fertility-preserving surgeryProcedure or 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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Neoadjuvant Chemotherapy; Drug: Immunotherapy; Procedure: Fertility-preserving surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 3 months
changes in tumor-related biomarkers
Measured: 3 months
Secondary outcomes (3)
OS (Overall Survival)
Measured: 2 years
DFS (Disease Free Survival)
Measured: 2 years
adverse events
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2025
- Study start15 Mar 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cervical CancersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Obstetrics & Gynecology Hospital of Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Keqin Hua, Obstetrics & Gynecology Hospital of Fudan University
- Investigators
- Keqin Hua, Doctor, Principal investigator, Gynecology and obstetrics hospital of fudan university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06878222
- Sponsor's protocol ID
- QIBA-CER-003
- Status last verified
- Mar 2025
- First submitted
- 10 Mar 2025
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Iparomlimab and Tuvonralimab Combined With Paclitaxel and Cisplatin as Neoadjuvant Therapy for Cervical Cancer: a Phase 2 Umbrella Trial
- ClinicalTrials.gov ID
- NCT06878222
- Acronym / sponsor ID
- QIBA-CER-003
- Conditions
- Cervical Cancers
- Keywords
- cervical cancer, neoadjuvant therapy, Iparomlimab and Tuvonralimab, immunotherapy, fertility-preserving
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Obstetrics & Gynecology Hospital of Fudan UniversityUniversity, hospital or other
- Study start
- 15 Mar 2025 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2030 (estimated)
- First posted
- 14 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In recent years, anti-PD-1/PD-L1 monoclonal antibodies, as a type of immunotherapy drug, have demonstrated promising anti-tumor efficacy in the treatment of cervical cancer patients. PD-1 (Programmed cell death protein 1) is a surface immune checkpoint protein that, by binding to its ligand PD-L1, inhibits the activation of T cells, thereby allowing tumor cells to evade immune system attacks. At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, a phase II clinical study was reported on the use of immunotherapy (sintilimab) combined with paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer. The results showed that the primary endpoint, pathological complete response (pCR), was 32.6% (14/43), and the best response rate (residual tumor infiltration depth less than 3 mm) was 51.2% (22/43).
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 produced as a single product from a single cell line. It offers the following advantages:
- Dual immune targets of PD-1 and CTLA-4 monoclonal antibodies: The anti-PD-1 antibody relieves T cell killing inhibition, while the anti-CTLA-4 antibody relieves T cell activation inhibition, working synergistically to enhance efficacy.
- Optimal 2:1 ratio of anti-PD-1 to anti-CTLA-4 antibodies: A dosing regimen of 5 mg/kg every 3 weeks ensures effective blood concentration, balancing efficacy and safety.
- Flexible antibody subtype design: The anti-PD-1 antibody uses the IgG4 subtype, which lacks ADCC (antibody-dependent cellular cytotoxicity) effects and does not deplete effector T cells. The anti-CTLA-4 antibody uses the IgG1 subtype, which has ADCC effects and can eliminate regulatory T cells, further enhancing efficacy.
- R255K mutation in the anti-CTLA-4 antibody: This mutation reduces the affinity of the anti-CTLA-4 antibody for the neonatal Fc receptor (FcRn), shortening its half-life to 1 week and lowering its blood concentration, thereby improving safety while maintaining efficacy.
Currently, Iparomlimab and Tuvonralimab for recurrent or metastatic cervical cancer as a second-line or later treatment has shown an objective response rate (ORR) of 33.8% and a progression-free survival (PFS) of 5.4 months, with a favorable safety profile. When combined with chemotherapy as first-line treatment for recurrent or metastatic cervical cancer, the ORR was 75.9%, PFS was 15.1 months, and immune-related adverse events occurred in 16.7% of cases. These results indicate that Iparomlimab and Tuvonralimab, both as monotherapy and in combination therapy, demonstrates significant anti-tumor activity and safety, suggesting that dual-target antibodies are effective for advanced cancer patients.
Therefore, given the urgent need to improve neoadjuvant therapy for locally advanced cervical cancer and neoadjuvant fertility-preserving therapy for early-stage cervical cancer, 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 locally advanced cervical cancer and fertility-preserving neoadjuvant therapy for cervical cancer. Additionally, the study aims to investigate the relationship between tumor-related biomarkers and the risk of recurrence, potentially offering new insights for optimizing fertility-preserving and non-preserving neoadjuvant therapies for cervical cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm1: locally advanced cervical cancer | Active comparator | Drug: Neoadjuvant Chemotherapy, Drug: Immunotherapy, Procedure: Radical surgeryPatients 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. |
| Arm2: cervical cancer patients desiring fertility-preserving treatment | Active comparator | Drug: Neoadjuvant Chemotherapy, Drug: Immunotherapy, Procedure: Fertility-preserving surgeryPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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).
- 3）Planned to undergo surgical treatments of cervical cancer.
- 4) -Arm 1 (Locally Advanced cervical cancer): Age 18-75 years.
- Arm2 (cervical cancer patients desiring fertility-sparing treatment): Age 18-45 years.
Key exclusion criteria (22 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neoadjuvant Chemotherapypaclitaxel, 135-175mg/m2, q3w, 3 cycles | Drug | Arm1: locally advanced cervical cancer, Arm2: cervical cancer patients desiring fertility-preserving treatment |
| Neoadjuvant Chemotherapycisplatin, 75-80mg/m2, q3w, 3 cycles | Drug | Arm1: locally advanced cervical cancer, Arm2: cervical cancer patients desiring fertility-preserving treatment |
| ImmunotherapyIparomlimab and Tuvonralimab, 5mg/kg, q3w, 3cycles | Drug | Arm1: locally advanced cervical cancer, Arm2: cervical cancer patients desiring fertility-preserving treatment |
| Radical surgeryAfter 3 cycles of neoadjuvant therapy, patients who achieved CR/PR will undergo radical hysterectomy plus lymphadenectomy | Procedure or surgery | Arm1: locally advanced cervical cancer |
| Fertility-preserving 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. | Procedure or surgery | Arm2: cervical cancer patients desiring fertility-preserving treatment |
Primary outcome
Objective Response Rate (ORR)
Time frame: 9 weeks
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)
Time frame: 3 months
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
Time frame: 3 months
3 secondary outcomes
OS (Overall Survival)
Time frame: 2 years
DFS (Disease Free Survival)
Time frame: 2 years
adverse events
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Keqin Hua, Doctor principal investigator
Gynecology and obstetrics hospital of fudan university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neoadjuvant Chemotherapy, Immunotherapy and Radical surgery in people with Cervical Cancers, run by Obstetrics & Gynecology Hospital of Fudan University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Junjun Qiu (18017738139, qiujunjun1113@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 9 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2025.