Iparomlimab and Tuvonralimab With Chemoradiation for the Treatment of Locally Recurrent and Oligometastatic Cervical Cancer

NCT06942416 | Recruiting Phase 2

• 1 other identifier: SDZLEC2025-028-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluation the efficacy and safety of iparomlimab and tuvonralimab, paclitaxel + cisplatin/carboplatin combined with radiotherapy of locally recurrent and oligometastatic cervical cancer.The main questions it aims to answer are:

• Receive iparomlimab and tuvonralimab, Paclitaxel + Cisplatin/Carboplatin and radiation therapy according to a specified protocol.
• Visit the clinic for regular checkups and tests throughout the treatment period.
• Be monitored for and have records kept of ORR, PFS, DCR, OS, and safety.
• Provide hematologic、tissue and stool samples to explore biomarkers. This study will help determine if this combination therapy can become a new standard of care for patients with locally recurrent and oligometastatic cervical cancer as well as identify biomarkers to better guide treatment strategies.

Conditions

Cervical Cancer; Neoplasm Recurrence, Local; Oligometastatic

Keywords

Immunotherapy; Paclitaxel; Cisplatin; Carboplatin; Radiation Therapy; Clinical Trials, Phase II as Topic; Progression-Free Survival; Biomarkers, Tumor; Treatment Outcome; Safety; Iparomlimab and Tuvonralimab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Progression-Free Survival (PFS) will be assessed from the date of enrollment until the date of first documented disease progression or death from any cause, whichever occurs first.

  Progression-Free Survival (PFS) will be assessed from the date of enrollment until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 60 months

Secondary Outcomes (4)

• Objective Response Rate

  Assessed every 6 weeks via imaging until study completion (up to 24 months

• Overall Survival

  The time interval from enrollment to death from any cause, assessed up to 60 months

• Disease Control Rate

  Assessed every 6 weeks via imaging until study completion (up to 24 months）

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Before each chemotherapy cycle (each cycle is 21 days), at 24 hours pre- and post-radiotherapy, and every 3 months during follow-up (up to 24 months)

Study Arms (1)

Chemotherapy+Immunotherapy+Radiotherapy

EXPERIMENTAL

Chemotherapy：TP (Paclitaxel and Cisplatin/Carboplatin); Immunotherapy：Iparomlimab and Tuvonralimab;Radiotherapy：All tumor lesions will be irradiated

Drug: Paclitaxel and Cisplatin/ Carboplatin; Drug: Iparomlimab and Tuvonralimab; Radiation: Radiotherapy

Interventions

Paclitaxel and Cisplatin/ Carboplatin DRUG

Paclitaxel and Cisplatin Paclitaxel: 135 mg/m², intravenous infusion, Day 1, every 3 weeks (Q3W). Cisplatin: 75 mg/m², intravenous infusion, Days 1-3, every 3 weeks (Q3W). Carboplatin 0.3-0.4g/m², intravenous infusion, Day 1, Q3W .Duration: 4-6 cycles.

Chemotherapy+Immunotherapy+Radiotherapy

Iparomlimab and Tuvonralimab DRUG

Iparomlimab and Tuvonralimab 5mg/kg, intravenous infusion, Day 1, Q3W. Duration: Continuous administration until disease progression, death, intolerable toxicity, subject's voluntary withdrawal, investigator's decision for withdrawal, or a maximum of 24 months.

Chemotherapy+Immunotherapy+Radiotherapy

Radiotherapy RADIATION

Site Selection: Original site, lymph nodes, lung metastasis, bone metastasis, adrenal metastasis, brain metastasis, and other relatively isolated, well-vascularized lesions. Select at least one suitable lesion for radiotherapy based on the impact of the recurrent or metastatic lesion on the body, prioritizing lesions that cause symptoms, are life-threatening, or are expected to cause symptoms.All tumor lesions will be irradiated, which can be done in phases. Dosage and Fractionation: Conventional or hypofractionated radiotherapy, with a biologically effective dose (BED) of ≥ 72 Gy. Dose adjustments can be made for brain metastases. Timing: After completing relevant baseline examinations, radiotherapy can be implemented generally after 4-6 cycles of systemic therapy, or after the first cycle for small, solitary metastatic lesions. echnique: IMRT, TOMO, SBRT, 3D-BT, interstitial implantation therapy, or proton therapy.

Chemotherapy+Immunotherapy+Radiotherapy

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent prior to any trial-related procedures;
• Female, aged ≥18 and ≤75 years;
• ECOG PS 0-1;
• Histologically or cytologically confirmed primary cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) at initial diagnosis, meeting clinical diagnostic criteria;
• Locally recurrent or oligometastatic cervical cancer after initial treatment. Total recurrent + metastatic lesions ≤5.Oligometastasis criteria:Lymph node metastases within the same region = 1 lesion;Liver metastases ≤1 lesion;Lung metastases ≤3 lesions
• At least one measurable lesion (including primary lesion) suitable for radiotherapy and evaluable per RECIST v1.1;
• Available tumor tissue sample for biomarker assessment;
• Expected survival ≥6 months;
• Normal organ function (within 7 days pre-enrollment):
• (1) Hematological criteria (no transfusion/granulocyte/platelet-stimulating drugs within 14 days):
• Hemoglobin (Hb) ≥80 g/L
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L
• Platelets (PLT) ≥50×10⁹/L (2) No functional organic disease:
• a) ALT/AST ≤2.5×ULN, total bilirubin ≤1.5×ULN, ALP ≤3×ULN, albumin ≥30 g/L b) Serum Cr ≤1.5×ULN (if \>1.5×ULN, CrCl ≥50 mL/min by Cockcroft-Gault formula) c) PT prolongation ≤6 sec, APTT ≤1.5×ULN d) TSH ≤ULN (if abnormal, FT3/FT4 must be normal) f) LVEF \>50% 10. Prior anti-tumor treatment toxicities recovered to ≤Grade 1 (CTCAE v5.0) pre-treatment, excluding:
• Alopecia/pigmentation (any grade)

You may not qualify if:

• Current use of immunosuppressants or systemic/absorbable topical corticosteroids (equivalent to \>10 mg/day prednisone) for immunosuppression, continued within 2 weeks before enrollment;
• History of Grade 3-4 immune-related adverse events (irAEs) associated with prior anti-tumor immunotherapy;
• Poorly controlled cardiac conditions:
• <!-- -->
• NYHA Class II or higher heart failure
• Unstable angina
• Myocardial infarction within 6 months
• Clinically significant supraventricular/ventricular arrhythmia requiring treatment
• QTc \>450 ms (males) or \>470 ms (females); 7. Coagulation abnormalities (INR \>1.5 or PT \>16 s), bleeding tendency, or current thrombolytic/anticoagulant therapy; 8. Prior radiotherapy/chemotherapy/hormonal therapy/surgery/targeted therapy completed \<4 weeks before study treatment (or \<5 drug half-lives, whichever is longer); unresolved toxicities (excluding alopecia) from prior therapies \>CTCAE Grade 1; 9. Poorly controlled third-space effusion requiring drainage before first trial drug administration; 10. Significant hemoptysis (≥2.5 mL/day) within 2 months before randomization; 11. Known hereditary/acquired bleeding/thrombotic disorders (e.g., hemophilia, coagulation dysfunction, thrombocytopenia, hypersplenism); 12. Active infection or unexplained fever \>38.5°C during screening/before first dose; 13. Objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or severe pulmonary dysfunction; 14. Immunodeficiency (e.g., HIV infection) or active hepatitis:
• HBV DNA \> upper limit of normal (ULN)
• HCV RNA \> ULN; 15. Use of other investigational drugs within 4 weeks before first dose; radiotherapy/local therapy within 2 weeks without full recovery; 16. Concurrent/prior malignancies (except cured basal cell carcinoma/cervical carcinoma in situ); 17. Planned concurrent systemic anti-tumor therapy during the study; 18. Live vaccination within 4 weeks before treatment or planned during the study; 19. Other conditions potentially requiring study termination per investigator judgment:
• Severe comorbidities (including psychiatric disorders) requiring treatment
• Critical lab abnormalities
• Social/family factors compromising safety or data/sample collection.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital Affiliated to Shandong First Medical University

Jinan, Shandong Recruiting, China

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Neoplasm Recurrence, Local; Neoplasms

Interventions

Paclitaxel; Cisplatin; Carboplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Therapeutics

Study Officials

• Peng Xie

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jing liu

CONTACT

+8613065077425; 13065077425@126.com

Study Design

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

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 24, 2025
• Study Start: February 28, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CN (1)