Efficacy and Safety of AK104 (PD-1/CTLA-4 Bispecial Antibody) Combined With Chemotherapy for Neoadjuvant Treatment of Advanced Ovarian Cancer

Phase 3

Not yet recruiting

• Conditions: Chemotherapy; Efficacy; Safety; Advanced Ovarian Cancer; AK104(PD-1/CTLA-4 Bispecial Antibody)
• Interventions: Drug: AK104

• Registration Number: NCT06542549
• Lead Sponsor: Anhui Provincial Hospital

Brief Summary

This is a randomized, controlled, single-center clinical study to evaluate AK104 in FIGO 2018 stage III-IV ovarian cancer subjects who were assessed to be at high perioperative risk and/or unable to achieve R0 resection prior to initial treatment. The efficacy and safety of neoadjuvant therapy with intravenous infusion combined with chemotherapy compared with chemotherapy alone.

Detailed Description

Subjects in the experimental group received AK104 combined chemotherapy for 3-4 cycles (determined by the investigator) before surgery, and subjects in the control group received chemotherapy for 3-4 cycles (determined by the investigator) before surgery. Treatment until unless intolerable toxicity occurs, informed consent is withdrawn, or other criteria for discontinuation are met.

The study treatment was followed by a 3-week treatment cycle. The dosing time window is ±3 days. Within 72 hours before each dosing cycle, subjects are required to complete various examinations, including vital signs, physical examination, laboratory examination, and physical status score, to evaluate the safety and tolerability of continued treatment.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-28
• Study First Submitted QC: 2024-08-03
• Last Update Submitted: 2024-08-03
• Study First Posted: 2024-08-07
• Last Update Posted: 2024-08-07
• Study Start: 2024-10-01
• Primary Completion: 2027-10-31
• Study Completion: 2030-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

1. Agree to sign the informed consent form.
2. 18 years ≤ age <75 years, female.
3. Patients with epithelial ovarian cancer (high-grade serous adenocarcinoma, ovarian endometrial carcinoid adenocarcinoma), peritoneal or fallopian tube carcinoma, or clear cell carcinoma confirmed by histopathology, FIGO 2018 stage III-IV.
4. Evidence of compliance with neoadjuvant chemotherapy for ovarian cancer: (a) Preoperative evaluation by gynecologic oncologists (multidisciplinary if necessary) indicates that R0 resection is less likely to be achieved after primary tumor reduction; (b) Patients whose physical state cannot tolerate PDS and are not suitable for immediate surgery (such as perioperative high risk, old age, medical complications, etc.); (c) Without any systematic anti-tumor therapy for ovarian cancer (including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy and immunotherapy); Note: Histopathology is obtained by puncture biopsy, laparoscopic exploration, etc. Lymph node resection or biopsy for clinical staging purposes is permitted.
5. Those with at least one measurable lesion (RECIST version 1.1).
6. ECOG Physical status score 0-2.
7. Estimated survival time > 12 weeks.
8. Good organ function.
9. Participants of reproductive age must agree to use effective contraception during the trial; Serum or urine pregnancy tests for women of childbearing age must be negative.
10. Non-lactating patients.

Exclusion Criteria

1. Ovarian cancer, fallopian tube cancer, primary peritoneal cancer (such as germ cell tumor) of non-epithelial origin; Ovarian tumors with low malignant potential (e.g., borderline tumors).
2. Patients with other malignant tumors in the past (within 5 years) or at the same time, with the exception of cured local tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ, etc.) and breast cancer with no recurrence >3 years after radical surgery.
3. Subjects with active viral hepatitis B, inactive or asymptomatic hepatitis B virus (HBV) carriers (HBV surface antigen [HBsAg] positive) with HBV DNA > 1000 IU/mL, and subjects with active viral hepatitis C. Note: Inactive or asymptomatic carriers, treated and stable hepatitis B subjects with HBV DNA ≤ 1000 IU/mL were admitted. Subjects with cured viral hepatitis C, HCVAb positive and HCV RNA negative were admitted.
4. A history of testing positive for known human immunodeficiency virus or known acquired immunodeficiency syndrome.
5. Have an active or possibly recurring autoimmune disease; The following are excluded: vitiligo, alopecia, psoriasis or eczema that do not require systematic treatment; Hypothyroidism due to autoimmune thyroiditis requires only stable dose hormone replacement therapy; Only a steady dose of insulin replacement is required for type 1 diabetes.
6. A history of severe allergic reactions to any monoclonal antibody and/or investigational drug ingredient.
7. Subjects with known active TB and suspected active TB should undergo clinical examination to rule out known active syphilis infection.
8. There is a history or current presence of noninfectious pneumonia/interstitial lung disease requiring systemic glucocorticoid therapy.
9. Severe infections occurring within 4 weeks prior to first dosing, including but not limited to active infections with comorbidification requiring hospitalization, sepsis, or severe pneumonia that received systemic anti-infective therapy within 2 weeks prior to first dosing (excluding antiviral therapy for hepatitis B or C).
10. Serious medical conditions or concomitant non-oncological conditions, such as neurological disorders, psychosis, infectious diseases, or laboratory abnormalities, may increase the risk of participating in the study or taking the investigational drug, which the investigator believes would make the patient unfit for entry into the study.
11. Patients with clinically significant cardiovascular disease.
12. Patients who were judged by the investigator to be unsuitable for this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AK104 combined with chemotherapy	AK104	10mg/kg, administered every three weeks. The drug was administered by intravenous infusion for 60 minutes (±10 minutes). For subjects who cannot tolerate a 60-minute infusion, the infusion time can be extended up to 120 minutes. Dose adjustment is not allowed during treatment; Delayed dosing is allowed.

Primary Outcome Measures

Name	Time	Method
R0 rate	Up to 6 months	Rate of complete tumor resection (R0): complete resection of the visible lesion.

Secondary Outcome Measures

Name	Time	Method
ORR	1 year	Objective tumor response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as best overall response according to radiological assessments.
DCR	1 year	Disease control rate (DCR) refers to the percentage of cases with remission and disease stability after treatment in the total number of evaluable cases.
PFS	1 year	Progress free survival is defined as the length of time from random assignment to disease progression or to death resulting from any cause other than the progress.
pCR	1 year	Pathological complete response is the breast primary focus and axillary lymph node surgery specimen pathological examination without invasive tumor cell residual.
AE	1 year	adverse events are evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.