Combination Therapy of AK112 With Chemotherapy and/or Olaparib in Platinum-sensitive Ovarian Cancer

Akeso

Status and phase: Enrolling; Phase 2

Conditions: Platinum-sensitive Ovarian Cancer

Treatments: Drug: AK112 high dose; Drug: Chemotherapy; Drug: AK112 low dose; Drug: Olaparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06686030

AK112-211

Details and patient eligibility

About

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

Full 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.

Enrollment: 150 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 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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150 participants in 5 patient groups

Cohort 1-10 (BRCAm)

Experimental group

Description:

AK112(10mg/kg)+chemo for 4-6 cycles, AK112 (10mg/kg)+Olaparib maintenance

Treatment:

Drug: Olaparib

Drug: AK112 low dose

Drug: Chemotherapy

Cohort 1-10B (non-BRCAm)

Experimental group

Description:

AK112(10mg/kg)+chemo for 4-6cycles, AK112(10mg/kg) maintenance

Treatment:

Drug: AK112 low dose

Drug: Chemotherapy

Cohort 1-20A (BRCAm)

Experimental group

Description:

AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg)+Olaparib maintenance

Treatment:

Drug: Olaparib

Drug: Chemotherapy

Drug: AK112 high dose

Cohort 1-20B (non-BRCAm)

Experimental group

Description:

AK112(20mg/kg)+chemo for 4-6cycles, AK112(20mg/kg) maintenance

Treatment:

Drug: Chemotherapy

Drug: AK112 high dose

Cohort 2 (Prior ≥2L)

Experimental group

Description:

AK112(20mg/kg)+Olaparib

Treatment:

Drug: Olaparib

Drug: AK112 high dose