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

Phase II, Single-Arm, Multicenter Clinical Study of Iparomlimab and Tuvonralimab in Combination With Paclitaxel Plus Cisplatin/Carboplatin and Radiotherapy for the Treatment of Locally Recurrent and Oligometastatic Cervical Cancer

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:

1. Does the combination therapy improve the overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety in participants?
2. What are the predictive biomarkers of treatment efficacy, and how can this information better guide the use of immune-oncology drugs in combination therapy?

Participants will:

• 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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Neoplasm Recurrence, Local; Oligometastatic
• Intervention / Treatment: Drug: Paclitaxel and Cisplatin/ Carboplatin; Drug: Iparomlimab and Tuvonralimab; Radiation: Radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jing liu; Phone Number: +8613065077425; Email: 13065077425@126.com

Study Locations

• China
  • Shandong Recruiting
    • Jinan, Shandong Recruiting, China
      • Recruiting
      • Shandong Cancer Hospital Affiliated to Shandong First Medical University
      • Contact: Jing Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed written informed consent prior to any trial-related procedures;
2. Female, aged ≥18 and ≤75 years;
3. ECOG PS 0-1;
4. Histologically or cytologically confirmed primary cervical cancer (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma) at initial diagnosis, meeting clinical diagnostic criteria;
5. 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
6. At least one measurable lesion (including primary lesion) suitable for radiotherapy and evaluable per RECIST v1.1;
7. Available tumor tissue sample for biomarker assessment;
8. Expected survival ≥6 months;
9. Normal organ function (within 7 days pre-enrollment):

(1) Hematological criteria (no transfusion/granulocyte/platelet-stimulating drugs within 14 days):

1. Hemoglobin (Hb) ≥80 g/L
2. Absolute neutrophil count (ANC) ≥1.5×10⁹/L
3. 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)
• Peripheral neuropathy (≤Grade 2)
• Other toxicities where benefit-risk favors treatment 11. Non-sterilized/childbearing-potential females must:
• Use medical contraception (IUD/oral contraceptives/condoms) during treatment + 3 months post-treatment
• Negative serum/urine HCG within 7 days pre-enrollment

• Non-lactating 12. Expected compliance with protocol follow-up following criteria:

  1. Prior immunotherapy (e.g., immune checkpoint inhibitors);
  2. Pathological diagnosis of gastric-type adenocarcinoma;
  3. Active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism). Exceptions: vitiligo; childhood asthma fully resolved without intervention in adulthood. Exclusion: asthma requiring bronchodilator therapy;
  4. Current use of immunosuppressants or systemic/absorbable topical corticosteroids (equivalent to >10 mg/day prednisone) for immunosuppression, continued within 2 weeks before enrollment;
  5. History of Grade 3-4 immune-related adverse events (irAEs) associated with prior anti-tumor immunotherapy;
  6. Poorly controlled cardiac conditions:
  1. NYHA Class II or higher heart failure
  2. Unstable angina
  3. Myocardial infarction within 6 months
  4. Clinically significant supraventricular/ventricular arrhythmia requiring treatment

  5. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time interval from enrollment to death from any cause	The time interval from enrollment to death from any cause, assessed up to 60 months
Objective Response Rate	ORR refers to the proportion of patients whose optimal response is complete or partial response	Assessed every 6 weeks via imaging until study completion (up to 24 months
Disease Control Rate	DCR refers to the proportion of patients whose optimal response is complete or partial response, or stable disease	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	Number of participants with adverse events and severe as assessed by CTCAE v5.	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)

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute
• Investigators: Principal Investigator: Peng Xie, Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 31, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Immunotherapy; Cisplatin; Carboplatin; Paclitaxel; Radiation Therapy; Treatment Outcome; Progression-Free Survival; Biomarkers, Tumor; Clinical Trials, Phase II as Topic; Iparomlimab and Tuvonralimab
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Uterine Diseases; Genital Diseases, Female; Neoplastic Processes; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Recurrence; Uterine Cervical Neoplasms; Neoplasm Recurrence, Local; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: SDZLEC2025-028-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No