Clinical trial NCT06686030: Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer
Official title: An Exploratory, Multi-cohort Phase II Study of Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Platinum-sensitive Ovarian Cancer
Keywords: platinum-sensitive ovarian cancer
PD-1
VEGF
antibody
AK112
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-11-13
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: An Exploratory, Multi-cohort Phase II Study of combination therapy of AK112 with chemotherapy and/or olaparib in platinum-sensitive ovarian cancer(PSOC)

Detailed description: This is a Phase 2, open label, multicohort, multicenter study designed to evaluate the efficacy and safety of combination of AK112 with chemotherapy and/or olaparib in platinum-sensitive ovarian cancer. AK112 is a bispecific monoclonal antibody targeting VEGF and PD-1.

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.

Primary outcomes:
measure: Progression-free survival (PFS) assessed by investigator per RECIST v1.1
timeFrame: up to 2 years
Secondary outcomes:
measure: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by investigator
timeFrame: Up to 2 years
measure: Disease control rate(DCR)assessed by investigator per RECIST v1.1
timeFrame: Up to 2 years
measure: Duration of Response (DOR) assessed by investigator per RECIST v1.1
timeFrame: Up to 2 years
measure: Time to Response (TTR) assessed by investigator per RECIST v1.1
timeFrame: Up to 2 years
measure: Overall Survival(OS)
timeFrame: Up to 2 years
measure: Number of participants with adverse event (AE)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science And Technology
Study officials:
References: