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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric and Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: cadonilimab; Drug: pulocimab; Drug: paclitaxel; Drug: placebo

• Study Type: Interventional
• Enrollment (Estimated): 506
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ting Liu; Phone Number: +86(0760)8987 3999; Email: clinicaltrials@akesobio.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Cancer Hospital & Institute
    • Contact: Lin Shen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cadonilimab in combination with pulocimab and paclitaxel; Cadonilimab (AK104) in combination with pulocimab (AK109) and paclitaxel, iv, every 3 weeks	Drug: cadonilimab; iv, q3w; Other Names: AK104; Drug: pulocimab; iv, q3w; Other Names: AK109; Drug: paclitaxel; iv, q3w
Active Comparator: Placebo in combination with paclitaxel; Placebo in combination with Paclitaxel, iv, every 3 weeks	Drug: paclitaxel; iv, q3w; Drug: placebo; iv, q3w

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by blinded independent central review (BICR)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first (based on RECIST 1.1 criteria).	Up to 2 years
Overall survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) assessed by investigator	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first (based on RECIST 1.1 criteria).	Up to 2 years
Objective Response Rate (ORR)	ORR is defined as proportion of subjects who have a complete or partial response relative to baseline according to RECIST 1.1 criteria	Up to 2 years
Duration of Response (DoR)	DoR is defined as the duration from the first documentation of objective response to the first documented disease progression(based on RECIST v1.1 criteria) or death due to any cause, whichever occurs first.	Up to 2 years
Disease control rate (DCR)	DCR is defined as the proportion of subjects with CR, PR, or SD (based on RECIST v1.1 criteria).	Up to 2 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Lin Shen, MD, Peking University Cancer Hospital & Institute; Principal Investigator: Xiaotian Zhang, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: March 26, 2024
• First Submitted That Met QC Criteria: March 26, 2024
• First Posted (Actual): April 2, 2024

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: AK109-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No