Perioperative Adebrelimab for Locally Advanced Cervical Cancer

Phase 2Not Yet RecruitingNCT07811375

Anhui Provincial Hospital35 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Locally Advanced Cervical Cancer

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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 Outcomes

Objective Response Rate (ORR)

Proportion of participants achieving complete response or partial response according to RECIST version 1.1.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.