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

Akeso

Status and phase: Not yet enrolling; Phase 2

Conditions: Recurrent Ovarian Cancer

Treatments: Drug: AK104; Drug: AK112; Drug: Chemotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT06560112

AK104-221

Details and patient eligibility

About

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

Full 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.

Enrollment: 172 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

172 participants in 4 patient groups

Cohort 1

Experimental group

Description:

AK104 q3w +Chemo

Treatment:

Drug: Chemotherapy

Drug: AK104

Cohort 2

Experimental group

Description:

AK112 q3w +Chemo

Treatment:

Drug: Chemotherapy

Drug: AK112

Cohort 3

Experimental group

Description:

AK112 q3w +AK104 q6w

Treatment:

Drug: AK112

Drug: AK104

Cohort 4

Experimental group

Description:

AK112 q3w +AK104 q6w +Chemo

Treatment:

Drug: Chemotherapy

Drug: AK112

Drug: AK104