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

Akeso

Status and phase: Active, not recruiting; Phase 3

Conditions: Cervical Cancer

Treatments: Drug: bevacizumab; Drug: carboplatin; Drug: cisplatin; Biological: AK104; Drug: Placebo; Drug: paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04982237

AK104-303

Details and patient eligibility

About

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

Enrollment: 445 patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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445 participants in 2 patient groups, including a placebo group

AK104+chemotherapy± bevacizumab

Experimental group

Description:

AK104 in combination with cisplatin or carboplatin and paclitaxel± bevacizumab

Treatment:

Drug: paclitaxel

Biological: AK104

Drug: cisplatin

Drug: bevacizumab

Drug: carboplatin

Placebo+chemotherapy± bevacizumab

Placebo Comparator group

Description:

Placebo in combination with cisplatin or carboplatin and paclitaxel± bevacizumab

Treatment:

Drug: Placebo

Drug: paclitaxel

Drug: cisplatin

Drug: bevacizumab

Drug: carboplatin