Overview
An Exploratory, Multi-cohort Phase II Study of Combination Therapy With AK104 and AK112 for Recurrent Ovarian Cancer
Description
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.
Eligibility
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.