A Study of AK104 Plus Platinum-containing Chemotherapy±Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer

Phase 3

Active, not recruiting

• Conditions: Cervical Cancer
• Interventions: Biological: AK104; Drug: paclitaxel; Drug: cisplatin; Drug: carboplatin; Drug: bevacizumab; Drug: Placebo

• Registration Number: NCT04982237
• Lead Sponsor: Akeso

Brief Summary

This is A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate AK104 Plus Platinum-containing Chemotherapy With or Without Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-21
• Study First Submitted QC: 2021-07-21
• Study First Posted: 2021-07-29
• Study Start: 2021-08-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-28
• Last Update Posted: 2025-03-04
• Primary Completion: 2025-04-01
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 445

Inclusion Criteria

1. signs the written informed consent form.

2. Women aged ≥ 18 and ≤ 75 years.

3. ECOG of 0 or 1.

4. Life expectancy ≥ 3 months.

5. Histologically or cytologically confirmed cervical cancer, not amenable to curative surgery or concurrent chemoradiotherapy.

   1. The histological types include squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma;
   2. No prior systemic therapy for persistent, recurrent or metastatic ([FIGO] Stage IVB) disease.

6. At least one measurable tumor lesion per RECIST v1.1; lesions at sites previously treated with radiotherapy or other loco-regional therapy are not considered as target lesions unless the lesion has unequivocal progression or the biopsy is obtained to confirm maligancy.

7. All subjects must provide archival tumor tissue samples within 2 years prior to randomization,or fresh tumor tissue samples obtained by biopsy.

8. Subjects must have adequate organ function as assessed in the laboratory tests.

9. Female subjects of childbearing potential must have a negative serum pregnancy test prior to the first dose. If a female subject of childbearing potential must use acceptable effective methods of contraception from screening and must agree to continue these precautions until 120 days after the last dose of study drug.

Exclusion Criteria

1. Subjects with other histopathological types of cervical cancer, such as small cell carcinoma, clear cell carcinoma, sarcoma, etc.
2. Clinically significant hydronephrosis that cannot be relieved by nephrostomy or ureteral stenting as judged by the Investigator.
3. Presence of nervous system (CNS) metastases or carcinomatous meningitis;
4. Subjects with uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
5. Patients with other active malignancies within 3 years prior to randomization.
6. Patients who have received other prior chemotherapeutic agents.
7. Any prior treatments targeting the mechanism of tumor immunity, such as anti-angiogenic therapy (e.g., bevacizumab), immune checkpoint inhibitors (e.g., anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), or therapy against immune costimulatory factors (e.g., antibodies directed against ICOS, CD40, CD137, GITR, OX40 targets, etc).
8. Major surgical treatment, open biopsy or significant trauma within 4 weeks prior to randomization; or elective major surgical treatment required during the study.
9. Active or potentially recurrent autoimmune disease.
10. 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;
11. Use of live vaccines within 4 weeks prior to randomization.
12. Known primary or secondary immunodeficiencies, including testing positive for human immunodeficiency virus (HIV) antibodies.
13. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
14. Known history of interstitial lung disease or non-infectious pneumonitis; unless induced by radiation therapies.
15. Serious infections requiring hospitalization.
16. Presence of active infection requiring systemic therapy.
17. Subjects with active hepatitis B and active viral hepatitis C.
18. Active or documented inflammatory bowel diseases, active diverticulitis.
19. Subjects with known history of severe hypersensitivity reactions to other monoclonal antibodies.
20. Known any contraindication to cisplatin/carboplatin, paclitaxel or allergy to any of their ingredients.
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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo+chemotherapy± bevacizumab	cisplatin	Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
Placebo+chemotherapy± bevacizumab	bevacizumab	Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
Placebo+chemotherapy± bevacizumab	Placebo	Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
AK104+chemotherapy± bevacizumab	AK104	AK104 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
AK104+chemotherapy± bevacizumab	carboplatin	AK104 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
AK104+chemotherapy± bevacizumab	cisplatin	AK104 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
AK104+chemotherapy± bevacizumab	paclitaxel	AK104 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
Placebo+chemotherapy± bevacizumab	paclitaxel	Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
Placebo+chemotherapy± bevacizumab	carboplatin	Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab
AK104+chemotherapy± bevacizumab	bevacizumab	AK104 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab

Primary Outcome Measures

Name	Time	Method
progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1	Up to approximately 2 years	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1
overall survival (OS)	Up to approximately 2 years	OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Number of subjects who develop detectable anti-drug antibodies (ADAs)	From first dose of AK104 through 90 days after last dose of AK104	The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs)
Time to Response（TTR Per RECIST 1.1 as Assessed by BICR	Up to approximately 2 years
Observed concentrations of AK104	From first dose of AK104 through 90 days after last dose of AK104	The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 2 years	Proportion of subjects who have a complete or partial response relative to baseline as assessed by investigator according to RECIST 1.1 criteria
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 2 years	Measured from the date of partial or complete response to therapy until the cancer progresses based on RECIST v1.1 criteria.
AE	Up to approximately 2 years	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment

Trial Locations

Locations (5)

The Second Affiliated Hospital,Anhui Medical University; 🇨🇳 Hefei, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, China

Women's Hospital School Of Medicine Zhejiang University; 🇨🇳 Hangzhou, China

Anhui Provincial Hospital; 🇨🇳 Hefei, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China