Combining AK112 with chemotherapy and Olaparib for ovarian cancer treatment

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

This study is testing if a new drug called AK112, when combined with chemotherapy and Olaparib, can help women with certain types of ovarian cancer feel better and improve their treatment outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Wuhan)
• Trial ID: NCT06686030 on ClinicalTrials.gov

What this trial studies

This Phase 2, open-label, multicohort study aims to evaluate the safety and efficacy of AK112, a bispecific monoclonal antibody targeting VEGF and PD-1, in combination with chemotherapy and/or Olaparib for patients with platinum-sensitive ovarian cancer. The study will involve female participants aged 18 and older who have histologically documented epithelial and non-mucinous platinum-sensitive ovarian cancer. Participants will receive either low or high doses of AK112 alongside standard chemotherapy and/or Olaparib, with the goal of assessing treatment outcomes based on measurable disease criteria.

Who should consider this trial

Good fit: Ideal candidates include female patients aged 18 and older with histologically confirmed platinum-sensitive ovarian cancer and adequate organ function.

Not a fit: Patients with non-epithelial or mucinous ovarian cancer, or those who have not previously received treatment with a PARPi if BRCA positive, may not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating ovarian cancer, indicating potential for success.

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 documented epithelial and non-mucinous PSOC. PSOC was defined as radiographic progression greater than 6 months from last dose of platinum-based chemotherapy.

   Note:
   1. If breast cancer susceptibility gene (BRCA) positive participants must have received prior treatment with a poly adenosine phosphate-ribose polymerase inhibitor (PARPi).
   2. Ovarian cancer includes ovarian cancer, fallopian tube cancer and primary peritoneal cancer in this study, unless otherwise specified.
6. Has measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 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, 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. Subjects with other active malignancies within 3 years prior to randomization.
5. Received systemic anti-tumor therapy within 2 weeks prior to randomization.
6. Any prior treatments targeting the mechanism of tumor immunity.
7. Major surgical , 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. Receiving 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. Subjects 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 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.
24. 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.

Where this trial is running

Wuhan

• Union Hospital Tongji Medical College Huazhong University of Science And Technology — Wuhan, China (Recruiting)

Study contacts

• Study coordinator: Ting Liu, M.D.

Conditions Platinum-sensitive Ovarian Cancer; platinum-sensitive ovarian cancer; PD-1; VEGF; antibody; AK112