Perioperative Adebrelimab for Locally Advanced Cervical Cancer

ConditionLocally Advanced Cervical Cancer

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexFemale

Age18-75

SponsorAnhui Provincial Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

Adebrelimab
Drug
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.
Paclitaxel
Drug
Paclitaxel 175 mg/m² will be administered intravenously every 3 weeks for three cycles as part of neoadjuvant treatment.
Cisplatin
Drug
Cisplatin 70-75 mg/m² will be administered intravenously every 3 weeks for three cycles as a platinum option during neoadjuvant treatment.
Carboplatin (AUC 5)
Drug
Carboplatin AUC 5 will be administered intravenously every 3 weeks for three cycles as an alternative platinum option during neoadjuvant treatment.

Treatment groups

35 Participants

are divided into 1 treatment group

Group A: Adebrelimab Plus Paclitaxel and Platinum-Based ChemotherapyExperimental treatment 4 interventions

Trial 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

Other outcomes

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.

Time frame

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.

Time frame

From baseline through maintenance treatment, with assessments every 3 months for up to 1 year after surgery

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Anhui Provincial Hospital

Lead sponsor

Source ClinicalTrials.gov

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