Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer

Официальное название

An Exploratory, Multi-cohort Phase II Study of Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer

Обзор

An Exploratory, Multi-cohort Phase II Study of combination therapy of AK112 with chemotherapy and/or olaparib in platinum-sensitive ovarian cancer(PSOC)

Подробное описание

This is a Phase 2, open label, multicohort, multicenter study designed to evaluate the efficacy and safety of combination of AK112 with chemotherapy and/or olaparib in platinum-sensitive ovarian cancer. AK112 is a bispecific monoclonal antibody targeting VEGF and PD-1.

Вмешательства

• Препарат AK112 low dose
  10mg/kg, Q3W, ivgtt
• Препарат Chemotherapy
  ivgtt
• Препарат Olaparib
  bid, oral
• Препарат AK112 high dose
  20mg/kg, Q3W, ivgtt

Первичные конечные точки

• Progression-free survival (PFS) assessed by investigator per RECIST v1.1 [Срок оценки: up to 2 years]

Вторичные конечные точки (6)

• Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by investigator [Срок оценки: Up to 2 years]
• Disease control rate(DCR)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 documented epithelial and non-mucinous PSOC. PSOC was defined as radiographic progression greater than 6 months from last dose of platinum-based chemotherapy.

Note:

• If breast cancer susceptibility gene (BRCA) positive participants must have received prior treatment with a poly adenosine phosphate-ribose polymerase inhibitor (PARPi).
• Ovarian cancer includes ovarian cancer, fallopian tube cancer and primary peritoneal cancer in this study, unless otherwise specified.
• Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 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, 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.
• Subjects with other active malignancies within 3 years prior to randomization.
• Received systemic anti-tumor therapy within 2 weeks prior to randomization.
• Any prior treatments targeting the mechanism of tumor immunity.
• Major surgical , 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.
• Receiving 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.
• Subjects 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 combination therapy-Related: For cohort 1: Known contraindications or allergy to paclitaxel or carboplatin. For Cohorts 1-10A, Cohort 1-20A, and Cohort 2: Known contraindications or allergy to Olaparib.
• Exclusion Criteria for AK112-Related: 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

• Union Hospital Tongji Medical College Huazhong University of Science And Technology — Ухань

Идентификаторы

NCT: NCT06686030 · AK112-211

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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