Clinical trial NCT06341335: A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma
Official title: A Randomized, Double-blind, Phase 3 Study Of Cadonilimab (AK104) Plus Pulocimab (AK109) And Paclitaxel Versus Paclitaxel In Patients With Advanced Gastric Or Gastroesophageal Junction Adenocarcinoma Who Failed First-line Immunochemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Gastric and Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2024-04-02
Enrollment: 506
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS) assessed by blinded independent central review (BICR)
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression-free survival (PFS) assessed by investigator
timeFrame: Up to 2 years
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
measure: Duration of Response (DoR)
timeFrame: Up to 2 years
measure: Disease control rate (DCR)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital & Institute
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Cancer Hospital & Institute
name: Xiaotian Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: