A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma

Akeso

Status and phase: Enrolling; Phase 3

Conditions: Gastric and Gastroesophageal Junction Adenocarcinoma

Treatments: Drug: paclitaxel; Drug: pulocimab; Drug: cadonilimab; Drug: placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06341335

AK109-301

Details and patient eligibility

About

This randomized, multicenter, double-blind, phase 3 study will evaluate the efficacy and safety of the combination of cadonilimab (AK104) and pulocimab (AK109) and paclitaxel compared with paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma who failed first-line immunochemotherapy.

Enrollment: 506 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Signed informed consent
2. Age ≥ 18 years and ≤ 75 years
3. Histologically or cytologically documented advanced unresectable or metastatic gastric adenocarcinoma or gastroesophageal Junction (GEJ) adenocarcinoma.
4. Failed first-line treatment with PD-(L)1 monoclonal antibody and standard chemotherapy
5. At least one measurable disease based on RECIST v1.1
6. ECOG status of 0 or 1
7. Estimated survival ≥ 3 months
8. Adequate organ function per protocol-defined criteria
9. Women of childbearing potential and men with female partners of childbearing potential must agree to use effective contraception during treatment and for at least 120 days following the last dose of study treatment

Exclusion criteria

1. Mixed gastric or gastroesophageal Junction cancer containing other pathological components than adenocarcinoma
2. HER2-positive
3. Known other invasive malignancies within 3 years
4. Subjects who are currently participating in other interventional study
5. Received prior systemic anti-tumour therapy within 4 weeks before randomization
6. Previous systemic treatment with taxane within 6 months before randomization
7. Previous systemic treatment targeting VEGF or anti-VEGFR signaling pathways
8. In addition to anti-PD-(L)1 monoclonal antibody, prior exposure to other immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy or other therapy that targets anti-tumor immune mechanisms
9. History of immune-related adverse effects leading to recommendation against reintroduction of immunotherapy or any condition dependency on systemic therapy with glucocorticoids or immunosuppressive agents within 14 days prior to randomization
10. History of severe infection within 4 weeks prior to randomization
11. Presence of central nervous system metastases, leptomeningeal metastases, or spinal cord compression
12. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage
13. History or presence of a serious hemorrhage or known bleeding tendency within 2 months before randomization
14. Major surgical procedure or serious trauma within 28 days prior to randomization
15. History of interstitial lung disease or noninfectious pneumonitis
16. Active infectious diseases, including tuberculosis, HIV infection, syphilis infection，or hepatitis B/C
17. Known allergy to the antibody or any component of the study drug; Or the constitution of being allergic to multiple substances
18. History of allogeneic organ transplantation or allogeneic haematopoietic stem cell transplantation
19. Toxicities of prior anticancer therapy have not resolved to ≤ Grade 1 (NCI-CTCAE version 5.0)
20. Use of live vaccines within 30 days prior to randomization
21. Pregnant or lactating women.
22. Any condition considered by the investigator to be inappropriate for enrollment

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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506 participants in 2 patient groups

Cadonilimab in combination with pulocimab and paclitaxel

Experimental group

Description:

Cadonilimab (AK104) in combination with pulocimab (AK109) and paclitaxel, iv, every 3 weeks

Treatment:

Drug: pulocimab

Drug: cadonilimab

Drug: paclitaxel

Placebo in combination with paclitaxel

Active Comparator group

Description:

Placebo in combination with Paclitaxel, iv, every 3 weeks

Treatment:

Drug: placebo

Drug: paclitaxel