Perioperative Adebrelimab for Locally Advanced Cervical Cancer (ADE-LACC)

A Single-Center, Single-Arm, Phase II Study of Perioperative Adebrelimab Combined With Neoadjuvant Paclitaxel and Platinum Chemotherapy in Locally Advanced Cervical Cancer

This prospective, single-center, single-arm, phase II study will evaluate perioperative adebrelimab in patients with locally advanced cervical cancer. Approximately 35 participants will receive three 3-week cycles of neoadjuvant adebrelimab in combination with paclitaxel and cisplatin or carboplatin. Participants without disease progression who are considered resectable will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last cycle of neoadjuvant treatment.

Postoperative treatment will be risk-adapted according to pathological risk factors. Participants with high-risk pathological factors will discontinue protocol treatment and receive standard concurrent chemoradiotherapy. Participants with intermediate-risk factors will receive guideline-recommended pelvic radiotherapy plus adebrelimab maintenance, whereas low-risk participants will receive adebrelimab maintenance. Adebrelimab maintenance will be administered every 3 weeks for up to 1 year and may be discontinued early after two consecutive negative circulating tumor HPV DNA tests at least 3 months apart.

The primary endpoint is the pathologic complete response rate. Secondary endpoints include objective response rate, disease control rate, disease-free survival, 2-year disease-free survival rate, overall survival, duration of response, quality of life, and safety. Dynamic circulating tumor HPV DNA will also be explored as a biomarker of treatment response and postoperative recurrence risk.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Cervical Cancer
• Intervention / Treatment: Drug: Adebrelimab; Drug: Paclitaxel; Drug: Cisplatin; Drug: Carboplatin (AUC 5)

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Zhou; Phone Number: 0551-62283954; Email: caddiezy@ustc.edu.cn

Study Locations

• China
  • Hefei, China
    • Anhui province hospital
    • Contact: Yi Liu; Phone Number: +8615755149324; Email: liuyi0428@mail.ustc.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 to 75 years.
• Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix; FIGO 2018 stage IB3 or IIA2, or carefully selected stage IIB or IIIC1r disease following multidisciplinary team evaluation, with a maximum primary tumor diameter ≥4 cm. For participants with stage IIB or IIIC1r disease, PET/CT or an equivalent staging examination must exclude para-aortic lymph node metastasis and distant metastasis, and definitive concurrent chemoradiotherapy must remain feasible if neoadjuvant treatment is ineffective.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Able to provide adequate tumor tissue for biomarker testing, defined as at least 18 qualified tissue sections.
• No prior surgery for cervical cancer, except staging procedures, and no prior radiotherapy, chemotherapy, systemic anticancer therapy, investigational therapy, or immunotherapy for cervical cancer.
• At least one measurable lesion according to RECIST version 1.1, defined as a tumor lesion with a longest diameter ≥10 mm on CT or a lymph node with a short-axis diameter ≥15 mm on CT.
• Estimated life expectancy ≥6 months.
• No primary or metastatic central nervous system disease.
• Adequate major organ function, meeting all of the following criteria:
• No blood or blood-product transfusion within 14 days before assessment;
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;
• Platelet count ≥80 × 10⁹/L;
• Hemoglobin ≥9 g/dL;
• Total bilirubin <1.5 × upper limit of normal (ULN);
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN;
• Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥40 mL/min calculated using the Cockcroft-Gault formula.
• Positive for high-risk human papillomavirus (HPV) DNA.
• Written informed consent provided and willingness to comply with protocol-required follow-up.

Exclusion Criteria:

• Considered unsuitable for participation in the study by the investigator.
• Known hypersensitivity or allergy to any study drug.
• Any active, known, or suspected autoimmune disease, including but not limited to interstitial pneumonitis, uveitis, enteritis, hepatitis, arthritis, nephritis, hypophysitis, hyperthyroidism, or hypothyroidism; vitiligo; or asthma requiring medical intervention with bronchodilators.
• Congenital or acquired immunodeficiency, including HIV infection, hepatitis B, or hepatitis C.
• Prior treatment with PD-1 and/or PD-L1 inhibitors, CTLA-4 antibodies, or other agents targeting immune-regulatory receptors.
• Current use of immunosuppressive agents. Patients in a stable condition who do not require systemic immunosuppressive therapy may be eligible.
• Long-standing unhealed wounds or fractures; major surgery, severe traumatic injury, fracture, or ulcer within 4 weeks before initiation of study treatment.
• Poorly controlled cardiac symptoms or cardiovascular disease, including New York Heart Association (NYHA) class III-IV heart failure or left ventricular ejection fraction (LVEF) <50%; abnormal coagulation function defined as INR >1.5 or APTT >1.5 × ULN with a bleeding tendency; or an arterial or venous thromboembolic event within 6 months before the first dose of study treatment.
• Symptomatic ascites, pleural effusion, or pericardial effusion requiring therapeutic puncture or drainage. Patients whose pleural or pericardial effusion remains stable for at least 2 weeks after drainage before the first dose of study treatment may be eligible.
• Central nervous system metastases.
• History of another malignancy, except for cured basal cell carcinoma of the skin or cervical carcinoma in situ.
• Pregnant or breastfeeding women.
• History of psychotropic drug abuse with inability to discontinue such use, or presence of a psychiatric disorder.

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: Adebrelimab Plus Paclitaxel and Platinum-Based Chemotherapy; Participants will receive three cycles of neoadjuvant adebrelimab (1200 mg intravenously every 3 weeks) plus paclitaxel (175 mg/m² intravenously every 3 weeks) and cisplatin (70-75 mg/m² intravenously every 3 weeks) or carboplatin (AUC 5 intravenously every 3 weeks). Participants considered suitable for R0 resection will undergo radical hysterectomy and pelvic lymph node dissection 28-42 days after the last neoadjuvant cycle. Postoperative management will be risk-adapted. Eligible intermediate- and low-risk participants will receive adebrelimab maintenance every 3 weeks for up to 1 year, with early discontinuation permitted after two consecutive negative ctHPV DNA tests at least 3 months apart

Drug: Adebrelimab; debrelimab 1200 mg will be administered intravenously every 3 weeks for three cycles during neoadjuvant treatment. Eligible participants will subsequently receive postoperative adebrelimab maintenance at 1200 mg intravenously every 3 weeks for up to 1 year, or until protocol-defined discontinuation criteria are met.; Drug: Paclitaxel; Paclitaxel 175 mg/m² will be administered intravenously every 3 weeks for three cycles as part of neoadjuvant treatment.; Drug: Cisplatin; Cisplatin 70-75 mg/m² will be administered intravenously every 3 weeks for three cycles as a platinum option during neoadjuvant treatment.; Drug: Carboplatin (AUC 5); Carboplatin AUC 5 will be administered intravenously every 3 weeks for three cycles as an alternative platinum option during neoadjuvant treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) Rate	The proportion of participants achieving pathologic complete response following neoadjuvant treatment. pCR is defined as no residual invasive carcinoma in the cervical primary tumor and no metastatic carcinoma in any resected regional lymph node, with ypT0/is ypN0 used as the operational definition. The primary analysis denominator will include all participants who receive at least one dose of study treatment. Participants who do not undergo surgery, experience disease progression, withdraw, die, or have missing primary endpoint data will be considered not to have achieved pCR.	At definitive surgery, planned 28-42 days after completion of the third cycle of neoadjuvant treatment (approximately 10-12 weeks after initiation of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Proportion of participants achieving complete response or partial response according to RECIST version 1.1.	From baseline to preoperative tumor assessment after completion of three cycles of neoadjuvant treatment, approximately 9 weeks
Disease Control Rate (DCR)	Proportion of participants achieving complete response, partial response, or stable disease according to RECIST version 1.1.	From baseline to preoperative tumor assessment after completion of three cycles of neoadjuvant treatment, approximately 9 weeks
Disease-Free Survival (DFS)	Time from definitive surgery to the first documented disease recurrence or death from any cause, whichever occurs first. Participants without an event will be censored at the date of the last known disease-free assessment.	From definitive surgery to disease recurrence, death, or last disease-free follow-up, assessed through December 31, 2029
Two-Year Disease-Free Survival Rate	Proportion of participants alive and free of disease recurrence 2 years after definitive surgery.	2 years after definitive surgery
Overall Survival (OS)	Time from the first administration of study treatment to death from any cause. Participants alive at the time of analysis will be censored at the date last known alive.	From first study treatment to death or last known alive, assessed through December 31, 2029
Duration of Response (DOR)	Among participants who achieve a complete or partial response, duration from the first documented response to disease progression or death before progression.	From first documented CR or PR to disease progression or death, assessed through December 31, 2029
Incidence of Adverse Events	Incidence and severity of adverse events, treatment-emergent adverse events, and serious adverse events, graded according to NCI CTCAE version 5.0.	From the first dose of study treatment through 90 days after the last dose or initiation of a new anticancer treatment, whichever occurs first
ORTC QLQ-C30 Scores Outcome	Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scores. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) is a 30-item questionnaire used to assess health-related quality of life in patients with cancer. Scores for each scale are linearly transformed to a range from 0 to 100. Higher scores on the functional scales and the global health status/quality-of-life scale indicate better functioning or quality of life, whereas higher scores on the symptom scales and single symptom items indicate greater symptom severity or problems. Change from baseline in EORTC QLQ-C30 scores will be assessed during study treatment.	Baseline and at the end of each 21-day treatment cycle during study treatment, through completion of study treatment, up to 1 year
EORTC QLQ-CX24 Outcome	Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module 24 (EORTC QLQ-CX24) Scores. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cervical Cancer Module 24 (EORTC QLQ-CX24) is a 24-item cervical cancer-specific quality-of-life questionnaire used in conjunction with the EORTC QLQ-C30. It assesses symptom experience, body image, sexual/vaginal functioning, lymphedema, peripheral neuropathy, menopausal symptoms, sexual worry, sexual activity, and sexual enjoyment. All scale and single-item scores are linearly transformed to a range from 0 to 100. Higher scores on symptom scales/items indicate greater symptom severity or problems, whereas higher scores for the functional items of sexual activity and sexual enjoyment indicate better functioning. Change from baseline in EORTC QLQ-CX24 scores will be assessed during study treatment.	Baseline and at the end of each 21-day treatment cycle during study treatment, through completion of study treatment, up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctHPV DNA Dynamics and Pathologic Response	Changes in circulating tumor HPV DNA status and levels from baseline to the preoperative and postoperative time points will be evaluated for their association with pathologic complete response.	At baseline, before surgery, and approximately 2 weeks after surgery
ctHPV DNA Dynamics and Disease-Free Survival	The association between longitudinal ctHPV DNA status and subsequent disease-free survival and 2-year disease-free survival will be explored. During maintenance treatment, ctHPV DNA will be assessed every 3 months. Two consecutive negative tests at least 3 months apart will define sustained molecular residual disease negativity according to the protocol.	From baseline through maintenance treatment, with assessments every 3 months for up to 1 year after surgery

Collaborators and Investigators

• Sponsor: Anhui Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 17, 2026
• First Submitted That Met QC Criteria: September 3, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; Minimal residual disease; Locally advanced cervical cancer; Pathologic complete response; Adebrelimab; Circulating tumor human papillomavirus DNA
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplastic Processes; Disease Progression; Pathological Conditions, Signs and Symptoms; Pathologic Complete Response; Neoplasm, Residual; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Carboplatin; Paclitaxel; Cisplatin
• Other Study ID Numbers: Zhouying-ZAT-2

Drug and device information, study documents

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