A Clinical Study of QL1706 Combined With Chemotherapy as Neoadjuvant Therapy for High-Risk Locally Advanced Cervical Cancer

A Randomized, Multicenter, Phase III Study of Iparomlimab and Tuvonralimab (QL1706) Combined With Chemotherapy as Neoadjuvant Therapy for Locally Advanced Cervical Cancer

This study aims to compare the efficacy and safety of "neoadjuvant immunotherapy combined with chemotherapy followed by immunotherapy combined with radiotherapy during the radiotherapy period" versus "standard concurrent chemoradiotherapy" in locally advanced cervical cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Cervical Carcinoma
• Intervention / Treatment: Radiation: standard EBRT+Brachytherapy; Drug: Cisplatin; Drug: Neoadjuvant chemoimmunotherapy; Radiation: Radiotherapy combined with immunotherapy; Drug: Immunomaintenance therapy

• Study Type: Interventional
• Enrollment (Estimated): 486
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Qin Xu; Phone Number: 13950419396; Email: xuqin@fjmu.edu.cn

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
      • Contact: Qin Xu; Phone Number: 13950419396; Email: xuqin@fjmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1) Age: 18-75 years; 2) Histologically confirmed cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma; 3) Locally advanced disease (Stage III-IVA per FIGO 2018 staging criteria, including IIIC1/IIIC2), confirmed by imaging evaluation; 4) ECOG performance status 0-1; 5) Expected to be able to complete external beam radiation therapy (EBRT) combined with brachytherapy; 6) No definite contraindications to radiotherapy; 7) Able to provide pathological specimens (≥18 qualified tissue slides) for biomarker testing; 8) No prior surgery, radiotherapy, chemotherapy, systemic therapy (including investigational drugs), or immunotherapy for cervical cancer; 9) At least one measurable lesion (per RECIST 1.1: ≥10 mm longest diameter for non-lymph node lesions on CT; ≥15 mm short axis for lymph node lesions on CT); 10) Expected survival ≥6 months; 11) Adequate major organ function. Hematology (without transfusion or blood products within 14 days): ANC ≥1.5×10⁹/L; platelets ≥80×10⁹/L; hemoglobin ≥9 g/dL. Biochemistry: total bilirubin <1.5×ULN; AST and ALT ≤2.5×ULN; serum creatinine ≤1.5×ULN, or creatinine clearance ≥40 mL/min (using the standard Cockcroft-Gault formula); 12) Participants have signed informed consent and agree to comply with follow-up; 13) Women of childbearing potential must agree to use effective contraception during the study and for at least 12 months after the last dose (postmenopausal women or women not of childbearing potential are exempt).

Exclusion Criteria:

• 1) Diagnosed with other malignancies within 5 years prior to first dose, excluding radically treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, radically excised carcinoma in situ, and/or papillary thyroid carcinoma; 2) Histologically confirmed small cell (neuroendocrine) cervical carcinoma, cervical carcinosarcoma, or gastric-type cervical adenocarcinoma; 3) FIGO 2018 Stage IVB disease; 4) Prior total hysterectomy (defined as removal of the entire uterus) or planned hysterectomy as part of initial cervical cancer treatment; 5) Bilateral hydronephrosis, unless at least one side has been stented or resolved by nephrostomy, or considered mild and not clinically significant by the investigator; 6) Anatomical or tumor geometric contraindications to intracavitary brachytherapy or combined intracavitary and interstitial brachytherapy, or any other contraindications; 7) Live vaccine administration within 30 days prior to first dose of study treatment; 8) Systemic immunostimulatory agents, colony-stimulating factors, interferons, interleukins, or vaccine combinations within 6 weeks or 5 half-lives (whichever is shorter) prior to Day 1 of Cycle 1; 9) Prior treatment with anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2) agents, or agents targeting other stimulatory or co-inhibitory T-cell receptors (e.g., CTLA-4, OX-40, CD137); 10) Systemic anti-cancer therapy within 4 weeks prior to randomization, including investigational drugs; 11) Currently participating in or previously participated in a study with an investigational drug; 12) Contraindications to cisplatin use; 13) Diagnosed with immunodeficiency or receiving chronic systemic corticosteroid therapy (>10 mg/day prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to first study treatment; 14) Hypersensitivity to any study drug; 15) Active autoimmune disease requiring systemic therapy within the past 2 years; 16) History of (non-infectious) pneumonitis/interstitial lung disease requiring corticosteroids, or current pneumonitis/interstitial lung disease; 17) Active infection requiring systemic treatment; 18) Known history of human immunodeficiency virus (HIV) infection; 19) Known history of hepatitis B or known active hepatitis C viral infection; 20) Any condition, treatment, laboratory abnormality, or other circumstance that may increase risk associated with study participation or administration of study treatment, or may interfere with interpretation of study results, and judged by the investigator or sponsor to render the participant unsuitable for this study; 21) Known psychiatric or substance abuse disorders that would interfere with the participant's ability to comply with study requirements; 22) Prior allogeneic tissue/solid organ transplantation; 23) Evidence of metastatic disease per RECIST 1.1, including lymph nodes in the inguinal region or above the level of the L1 vertebral body; 24) Women with pregnancy desire, pregnant women, or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard concurrent chemoradiotherapy（CCRT）; Accept standard concurrent chemoradiotherapy	Radiation: standard EBRT+Brachytherapy; EBRT: 45-50.4Gy, Brachytherapy: 6Gy ×5; Drug: Cisplatin; Cisplatin 40mg/m2, qw×5
Experimental: Neoadjuvant Therapy Group; Participants in the experimental arm will receive 2 cycles of QL1706 + paclitaxel (albumin-bound) + Cisplatin/Carboplatin. Following neoadjuvant therapy, patients will undergo EBRT + QL1706. After EBRT completion, patients with clinical complete response (CCR) will receive brachytherapy at a dose of 600 cGy × 3 fractions; patients without CCR will receive brachytherapy at a dose of 600 cGy × 5 fractions. Subsequent sequential QL1706 will be administered for up to 2 years, until disease progression, or unacceptable toxicity.	Drug: Neoadjuvant chemoimmunotherapy; Neoadjuvant phase: total of 2 cycles. Iparomlimab/Tuvonralimab 5mg/kg,D1,Q3W + albumin paclitaxel 90mg/m2, D1、8、15，Q3W+ Cisplatin 25mg/m2 or Carboplatin AUC = 1.5 , D1、8、15，Q3W; Radiation: Radiotherapy combined with immunotherapy; Following neoadjuvant therapy, patients will receive EBRT + QL1706. After EBRT completion, brachytherapy dose is 600 cGy × 3 fractions for patients with clinical complete response (CCR), and 600 cGy × 5 fractions for non-CCR patients.; Drug: Immunomaintenance therapy; Iparomlimab/Tuvonralimab (QL1706) 5 mg/kg，D1,Q3W. Will be administered for up to 2 years, until disease progression, or until unacceptable toxicity, whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival（PFS）	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first.	Up to approximately 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 60 months
Objective Response Rate (ORR)	ORR is defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed investigator per RECIST 1.1	Up to approximately 60 months
Disease Control Rate (DCR)	DCR is defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by investigator per RECIST 1.1	Up to approximately 3 years
Clinical Complete Response Rate, CCR	Defined as the absence of measurable tumor lesions on clinical examination and imaging assessment, which may be adjunctively confirmed by necessary pathological examinations (such as cervical biopsy). CCR is primarily used to guide brachytherapy dose stratification and is not used as a criterion for PFS event determination.	Up to approximately 6 months
Duration of Response (DOR)	Assessed by investigators	Up to approximately 3 years
Time to Response (TTR)	Assessed by investigators	Up to approximately 3 years
Time to Progression (TTP)	Assessed by investigators	Up to approximately 3 years
Quality of Life Assessed by Patient-Reported Outcome Questionnaires (QoL)	Quality of life will be assessed using EORTC QLQ-C30, EORTC QLQ-CX24, and EQ-5D questionnaires.	Up to approximately 3 years
Incidence of brachytherapy dose reduction	Defined as the proportion of participants who, after completion of external beam radiotherapy (EBRT) and originally planned to receive the standard brachytherapy dose regimen (5 fractions), achieved the predefined clinical complete response (CCR) criteria and, upon investigator assessment, actually received a reduced number of brachytherapy fractions (3 fractions).	Up to approximately 6 months
Percentage of Participants With Adverse Events (AEs)	Number of participants with adverse events (AEs) according to CTCAE 5.0	Up to approximately 3 years

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 31, 2032
• Study Completion (Estimated): August 31, 2032

Study Registration Dates

• First Submitted: May 22, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 22, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Biological Therapy; Immunomodulation; Cisplatin; Immunotherapy
• Other Study ID Numbers: QL-CC-QIBA-3078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because of privacy protection and ethical restrictions. Deidentified aggregate results may be shared in publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No