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

Официальное название

A Single-Arm, Open- Label, Multicenter Phase II Study 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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат Disitamab Vedotin
  2.0 mg/kg IV every 2 weeks
• Препарат Zimberelimab
  240mg IV every 2 weeks

Первичные конечные точки

• Safety run-in ：Safety(adverse event) [Срок оценки: Up to approximately 2 years]
• Dose extension period ：Objective Response Rate (ORR) [Срок оценки: Up to approximately 2 years]

Вторичные конечные точки (5)

• Objective Response Rate(ORR) [Срок оценки: Up to approximately 2 years]
• Duration of Response (DOR) [Срок оценки: Up to approximately 2 years]
• Disease Control Rate(DCR) [Срок оценки: Up to approximately 2 years]
• Progression-free survival (PFS), evaluated by the investigator [Срок оценки: Up to approximately 2 years]
• Overall survival (OS) [Срок оценки: Up to approximately 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 12 центров

• The first affiliated hospital of bengbu medical college — Bengbu
• Beijing Obstetrics and Gynecology Hospital ,Capital Medical University — Пекин
• Chongqing University Cancer Hospital — Чунцин
• Guangxi Tumor Hospital — Nanning
• Hunan Cancer Hospital — Чанша
• Jiangxi Maternal and Child Health Hospital — Nanchang
• Liaoning Cancer Hospital & Institute — Шэньян
• Shandong Cancer Hospital & Institute — Цзинань
• … и ещё 4 центра

Идентификаторы

NCT: NCT06155396 · RC48-C030

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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