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

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

Study Overview

• Status: Recruiting
• Conditions: Recurrent Ovarian Cancer
• Intervention / Treatment: Drug: AK104; Drug: Chemotherapy; Drug: AK112

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 172
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Liu, M.D.; Phone Number: (0760)89873999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Xiaohua Wu, MD
    • Principal Investigator: Xiaohua Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; AK104 q3w +Chemo	Drug: AK104; ivgtt; Other Names: Cadonilimab; Drug: Chemotherapy; ivgtt; Other Names: Monotherapy Non-Platinum Chemotherapy chosen by the investigator
Experimental: Cohort 2; AK112 q3w +Chemo	Drug: Chemotherapy; ivgtt; Other Names: Monotherapy Non-Platinum Chemotherapy chosen by the investigator; Drug: AK112; ivgtt; Other Names: Ivonescimab
Experimental: Cohort 3; AK112 q3w +AK104 q6w	Drug: AK104; ivgtt; Other Names: Cadonilimab; Drug: AK112; ivgtt; Other Names: Ivonescimab
Experimental: Cohort 4; AK112 q3w +AK104 q6w +Chemo	Drug: AK104; ivgtt; Other Names: Cadonilimab; Drug: Chemotherapy; ivgtt; Other Names: Monotherapy Non-Platinum Chemotherapy chosen by the investigator; Drug: AK112; ivgtt; Other Names: Ivonescimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by investigator	Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS) assessed by investigator per RECIST v1.1	PFS is defined as the time from the date of first dosing till the first documented disease progression (Per RECIST v1.1 assessed by the investigator) or death due to any cause, whichever occurs first.	Up to 2 years
duration of Response (DOR) assessed by investigator per RECIST v1.1	DOR means time measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria.	Up to 2 years
Time to Response (TTR) assessed by investigator per RECIST v1.1	TTR refers to Time to Response.	Up to 2 years
Overall Survival(OS)	OS is defined as the time from randomization or first dosing to death due to any cause.	Up to 2 years
Number of participants with adverse event (AE)	The number of participants experiencing an Adverse Event (AE) and the severity of AEs will be assessed. AE refers to any untoward medical occurrence or deterioration of existing medical event after the subject signed the ICF, whether or not considered related to the study treatment.	Up to 2 years

Collaborators and Investigators

• Sponsor: Akeso

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Carcinoma, Ovarian Epithelial; Recurrence; Ovarian Neoplasms
• Other Study ID Numbers: AK104-221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No