A Study of RC48-ADC Combination With Zimberelimab Injection Therapies at Least First-line Platinum-containing Standard Therapy Failed With Recurrent or Metastatic Cervical Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy,safety of RC48-ADC in Combination with Zimberelimab Injection for the Treatment ,at least first-line platinum-containing standard therapy failed in HER2-expressing subject with Recurrent or Metastatic Cervical Cancer

Detailed Description
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This is a Phase II, Single-Arm ,multicenter, open-label clinical trial designed to evaluate safety and efficacy of RC48-ADC in Combination with Zimberelimab Injection for the Treatment ,at least first-line platinum-containing standard therapy failed in HER2-expressing subject with Recurrent or Metastatic Cervical Cancer.The HER2-expressing is defined as: the HER2 IHC 3+ or 2+, or 1+.subjects with IHC 2+ require testing for FISH.

Official Title
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A Single-Arm, Open- Label, Multicenter Phase II Study of RC48-ADC Vedicilumab for Injection in Combination With Zimberelimab Injection for the Treatment ,at Least First-line Platinum-containing Standard Therapy Failed in HER2-expressing Subject With Recurrent or Metastatic Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: Disitamab Vedotin
* Drug: Zimberelimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: a)Patients with histologically confirmed HER2-expressing recurrent or metastatic cervical cancer who have failed at least 1 line of standard platinum-containing therapy ; b) Not suitable for surgery or radiotherapy; Voluntarily agreed to participate in the study and signed an informed consent form. Female, age ≥ 18 years Expected survival ≥ 12 weeks Central laboratory confirmation of HER2 expression: IHC 1+, 2+, or 3+; subjects with IHC 2+ require testing for FISH. Central laboratory confirmation of PD-L1 expression Measurable disease according to RECIST 1.1 standard ECOG physical condition 0 or 1 point Adequate organ function, criteria should be met during the screening period ANC ≥1,500/µL platelet count ≥100,000/μL hemoglobin ≥9.0 g/dL total bilirubin ≤1.5 × upper limit normal (ULN) OR direct bilirubin ≤ULN for subjects with total bilirubin >1.5 × ULN. Serum bilirubin ≤3× ULN for subjects with Gilbert's disease CrCl ≥50 mL/min (measured by the Cockcroft-Gault formula as applicable, or 24-hour urine). ALT and AST ≤2.5× ULN without liver metastases or ≤5× ULN with liver metastases LVEF ≥>50% Female subjects should be surgically sterilised, post-menopausal or agree to use at least one medically approved contraceptive method during and for 6 months after the end of the study treatment period, must have had a negative blood pregnancy test within 7 days prior to study entry, and must be non-lactating. Willingness and ability to comply with trial and follow-up procedure arrangements. Exclusion Criteria: Have central nervous system metastases and/or carcinomatous meningitis. Received anti-tumour therapy or participated in another clinical study treatment within 4 weeks prior to the start of study treatment. Toxicity due to previous antineoplastic therapy has not recovered to NCI-CTCAE (version 5.0) grade 0-1. Major surgery with incomplete recovery within 4 weeks prior to start of study dosing. Serum virology examination (based on the normal value of the research center) : HBsAg test results were positive, and HBV DNA copy number was positive; HCVAb test results were positive (HCV RNA PCR test results were negative only to be included in this study); HIVAb tested positive Have received a live or live attenuated vaccine within 4 weeks prior to the start of study dosing; or plan to receive any vaccine during the study period Grade 3 or higher heart failure History of gastrointestinal perforation and/or fistula within the previous 6 months Serious arterial/venous thrombotic event or cardiovascular accident within 1 year prior to study drug administration Presence of active or progressive infection requiring systemic therapy, with severe infection within 4 weeks prior to first dose; Active TB. Presence of systemic disease not under stable control as judged by the investigator. History of interstitial pneumonia, obstructive lung disease, drug-induced pneumonia, radiation pneumonia, idiopathic pneumonia or active pneumonia. Clinically relevant pyelonephrosis cannot be alleviated by ureteral stents or percutaneous drainage. Presence of active autoimmune disease requiring systemic therapy within 2 years prior to the start of study drug administration, allowing for relevant alternative therapy. Other malignancy within 5 years prior to start of study drug administration. Previous allogeneic haematopoietic stem cell transplantation. Previous treatment with other Antibody-drug conjugateantibody-coupled drugs. Known hypersensitivity to the drug vedicilizumab for injection and its components or to Zimberelimab injection and other monoclonal antibodies. Have any other disease, metabolic abnormality, physical examination abnormality or laboratory test abnormality. Estimated lack of patient adherence to participate in this clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Disitamab Vedotin + Zimberelimab<br>Disitamab Vedotin（RC48-ADC）with Zimberelimab arm | Drug: Disitamab Vedotin<br>* 2.0 mg/kg IV every 2 weeks<br>* Other names: Disitamab Vedotin （RC48-ADC);Drug: Zimberelimab<br>* 240mg IV every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety run-in ：Safety(adverse event) | to evaluate safety including adverse event rate and adverse event grade. | Up to approximately 2 years | 
| Dose extension period ：Objective Response Rate (ORR) | The objective response rate will be mainly analyzed by according to the RECIST 1.1 standard tumor evaluation by the investigator will be performed | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | The objective response rate will be mainly analyzed by according to the RECIST 1.1 standard tumor evaluation by the investigator will be performed | Up to approximately 2 years | 
| Duration of Response (DOR) | DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death | Up to approximately 2 years | 
| Disease Control Rate(DCR) | Proportion of patients whose tumors shrank or stabilized for a certain period of time | Up to approximately 2 years | 
| Progression-free survival (PFS), evaluated by the investigator | Progression-free survival (PFS) refers to the time from the date of first administration to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard. | Up to approximately 2 years | 
| Overall survival (OS) | Overall survival (OS) refers to the time from the date of first administration to the date of death of the subject. | Up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-expressing, Recurrent Cervical Cancer, Metastatic Cervical Cancer