An Exploratory, Multi-cohort Phase II Study of Combination Therapy With AK104 and AK112 for Recurrent Ovarian Cancer

Обзор

An Exploratory, Multi-cohort Phase II Study of Combination Therapy With AK104 and AK112 for Recurrent Ovarian Cancer

Подробное описание

This is a Phase 2, open label, multicohort, multicenter study designed to evaluate the efficacy and safety of combination therapy of AK104, AK112 and chemotherapy in recurrent ovarian cancer.

AK104 is a bispecific monoclonal antibody targeting both CTLA-4 and PD-1. AK112 is a bispecific monoclonal antibody targeting VEGF and PD-1.

Вмешательства

• Препарат AK104
  ivgtt
• Препарат AK112
  ivgtt
• Препарат Chemotherapy
  ivgtt

Первичные конечные точки

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by investigator [Срок оценки: Up to 2 years]

Вторичные конечные точки (5)

• progression-free survival (PFS) assessed by investigator per RECIST v1.1 [Срок оценки: Up to 2 years]
• duration of Response (DOR) assessed by investigator per RECIST v1.1 [Срок оценки: Up to 2 years]
• Time to Response (TTR) assessed by investigator per RECIST v1.1 [Срок оценки: Up to 2 years]
• Overall Survival(OS) [Срок оценки: Up to 2 years]
• Number of participants with adverse event (AE) [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• Signs the written informed consent form.
• Female participants who are at least 18 years of age on the day of signing informed consent with.
• ECOG of 0 or 1.
• Life expectancy ≥ 3 months.
• Histologically diagnosed high-grade epithelial ovarian cancer (including high-grade serous, clear cell, G3 endometrioid) that has relapsed after platinum-containing standard chemotherapy.

• Recurrence of Platinum-sensitive (relapse ≥6 months after the end of platinum-containing therapy) who is not suitable for platinum-containing therapy after ≥ 3 lines of therapy;
• Recurrence of platinum resistance , ≤3 previous lines of therapy. Note: Ovarian cancer includes ovarian cancer, fallopian tube cancer and primary peritoneal cancer in this study, unless otherwise specified.
• Has measurable disease based on RECIST v1.1 as determined by the site study team.
• Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.
• Has adequate organ function.
• All subjects of reproductive potential must agree to use an effective method of contraception, during and for 6 months after the last dose of study treatment.

Критерии исключения

• Other pathological types such as mucinous cancer, low-grade serous carcinoma, carcinosarcoma, sex cord stromal cell tumor, etc.
• Presence of central nervous system (CNS) metastases or carcinomatous meningitis.
• Subjects with uncontrollable pleural, pericardial, or peritoneal effusion requiring repeated drainage.
• Patients with other active malignancies within 3 years prior to randomization.
• Received systemic anti-tumor therapy within 3 weeks prior to randomization.
• Any prior treatments targeting the mechanism of tumor immunity.
• Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to randomization; or elective major surgical treatment required during the study.
• Active or potentially recurrent autoimmune disease.
• Subjects who require systemic treatment with glucocorticoid (> 10 mg/day of prednisone or equivalent glucocorticoid) or other immunosuppressive agents within 14 days prior to randomization.
• Use of live vaccines within 4 weeks prior to randomization.
• Known primary or secondary immunodeficiencies, including testing positive for human immunodeficiency virus (HIV) antibodies.
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Known history of interstitial lung disease or non-infectious pneumonitis.
• Serious infections requiring hospitalization.
• Presence of active infection requiring systemic therapy.
• Subjects with active hepatitis B and active viral hepatitis C.
• Active or documented inflammatory bowel diseases, active diverticulitis.
• Patients with clinically significant cardio-cerebrovascular disease.
• Unresolved toxicities from prior anticancer therapy.
• History of severe hypersensitivity reactions to other mAbs.
• Pregnant or lactating women.
• Any condition that, in the opinion of the Investigator, may result in a risk when receiving the study drug.
• Exclusion Criteria for Chemotherapy-Related Cohorts (Cohorts 1,2,4): Known contraindications or allergy to PLD, paclitaxel or topotecan.
• Exclusion Criteria for AK112-Related Cohorts (Cohorts 2,3,4): Known contraindications or allergy to any component of VEGF mABs or any medical conditions that affect the safety of AK112.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06560112 · AK104-221

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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