Combination therapy for recurrent ovarian cancer

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

This study is testing a new combination of treatments for women with recurrent ovarian cancer to see if it can help them feel better and improve their outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 172 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Shanghai)
• Trial ID: NCT06560112 on ClinicalTrials.gov

What this trial studies

This Phase 2, open-label, multicohort study aims to evaluate the efficacy and safety of a combination therapy involving AK104, AK112, and chemotherapy in patients with recurrent ovarian cancer. AK104 is a bispecific monoclonal antibody targeting CTLA-4 and PD-1, while AK112 targets VEGF and PD-1. The study will enroll female participants who have histologically diagnosed high-grade epithelial ovarian cancer that has relapsed after standard chemotherapy. Participants will be monitored for treatment response and safety outcomes throughout the study.

Who should consider this trial

Good fit: Ideal candidates include female patients aged 18 and older with high-grade epithelial ovarian cancer that has relapsed after platinum-containing chemotherapy.

Not a fit: Patients with low-grade ovarian cancer or those who have not received prior platinum-containing therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with recurrent ovarian cancer.

How similar studies have performed: Other studies involving combination therapies targeting similar pathways have shown promising results, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

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

   1. 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;
   2. 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.
6. Has measurable disease based on RECIST v1.1 as determined by the site study team.
7. Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue.
8. Has adequate organ function.
9. 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:

1. Other pathological types such as mucinous cancer, low-grade serous carcinoma, carcinosarcoma, sex cord stromal cell tumor, etc.
2. Presence of central nervous system (CNS) metastases or carcinomatous meningitis.
3. Subjects with uncontrollable pleural, pericardial, or peritoneal effusion requiring repeated drainage.
4. Patients with other active malignancies within 3 years prior to randomization.
5. Received systemic anti-tumor therapy within 3 weeks prior to randomization.
6. Any prior treatments targeting the mechanism of tumor immunity.
7. Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to randomization; or elective major surgical treatment required during the study.
8. Active or potentially recurrent autoimmune disease.
9. 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.
10. Use of live vaccines within 4 weeks prior to randomization.
11. Known primary or secondary immunodeficiencies, including testing positive for human immunodeficiency virus (HIV) antibodies.
12. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
13. Known history of interstitial lung disease or non-infectious pneumonitis.
14. Serious infections requiring hospitalization.
15. Presence of active infection requiring systemic therapy.
16. Subjects with active hepatitis B and active viral hepatitis C.
17. Active or documented inflammatory bowel diseases, active diverticulitis.
18. Patients with clinically significant cardio-cerebrovascular disease.
19. Unresolved toxicities from prior anticancer therapy.
20. History of severe hypersensitivity reactions to other mAbs.
21. Pregnant or lactating women.
22. Any condition that, in the opinion of the Investigator, may result in a risk when receiving the study drug.
23. Exclusion Criteria for Chemotherapy-Related Cohorts (Cohorts 1,2,4): Known contraindications or allergy to PLD, paclitaxel or topotecan.
24. 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.

Where this trial is running

Shanghai

• Fudan University Shanghai Cancer Center — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Ting Liu, M.D.

Conditions Recurrent Ovarian Cancer