Gastric / Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Gastric/GEJ adenocarcinoma, gastric cancer, cadonilimab, nivolumab, chemotherapy, HER2-negative cancer, Immunotherapy
Brief summary
The goal of this randomized, double-blind, multi-regional phase 3 study of cadonilimab combined with chemotherapy versus chemotherapy in combination with or without nivolumab for the first-line treatment of participants with HER2-negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma trial is to compare OS between cadonilimab combined with chemotherapy and chemotherapy in combination with or without nivolumab in the ITT population.
Interventions
DRUGCadonilimab
Anti-PD-1/ CTLA-4 tetrameric bispecific antibody
DRUGCAPOX regimen
A combination treatment contains oxaliplatin and capecitabine
DRUGNivolumab
Anti-PD-1 monoclonal antibody
DRUGPlacebo
Placebo
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to provide written informed consent and can understand and comply with the requirements of the study. 2. Histopathologically-confirmed diagnosis of locally advanced unresectable or metastatic G/GEJ adenocarcinoma. 3. No prior systemic therapy for locally advanced unresectable or metastatic G/GEJ adenocarcinoma. NOTE: For participants who have received prior neoadjuvant/adjuvant therapy for curative intent, the time between disease progression and last treatment should be at least 6 months. 4. ECOG PS of 0 or 1 within 3 days prior to randomization. 5. Age ≥ 18 years at the time of voluntarily signing informed consent. 6. Evaluable PD-L1 expression results. 7. Participants must have at least one measurable lesion per RECIST v1.1 as assessed by investigator assessment. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 8. Adequate organ function as indicated by the following laboratory values. Specimens must be collected within 7 days prior to the first dose of study treatment. 9. Life expectancy ≥3 months. 10. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception during treatment, and for at least 150 days after the last dose of cadonilimab/nivolumab, 270 days after the last dose of oxaliplatin, and 180 days after the last dose of capecitabine. 11. Non-sterile males must agree to use effective contraception during treatment and for at least 120 days following the last dose of cadonilimab/nivolumab/capecitabine and 180 days after the last dose of oxaliplatin.
Exclusion criteria
1. Histopathologically confirmed other pathological types, such as squamous cell carcinoma, sarcoma or undifferentiated carcinoma. 2. Known HER2 positive. Be HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH). 3. Participants with active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. 4. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1 time/month). 5. Clinically significant bleeding symptoms within 28 days before the first dose or a definite tendency to bleed. 6. Have a history of ≥ Grade 2 gastrointestinal perforation and/or fistulae (including prior gastric fistula operation) within 6 months prior to randomization. 7. Participants who, in the opinion of the investigator, have symptoms or signs suggestive of clinically unacceptable deterioration of the primary disease at the time of screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Approximately up to 14months | Time from randomization to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival(PFS) | Approximately up to 8 months | Time from the date of randomization to the date of progressive disease or death from any cause, whichever occurs first. |
| Objective response rate (ORR) | Approximately up to 8 months | — |
| Disease control rate (DCR) | Approximately up to 8 months | — |
| Duration of response (DoR) | Approximately up to 8 months | — |
| Safety assessment | Approximately up to 18 months | Incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results |
Countries
China, Germany, Poland, United States
Contacts
CONTACTZhifang Yao, MD
CONTACTYelena Janjigian, MD
PRINCIPAL_INVESTIGATORJiafu Ji, MD
Peking University Cancer Hospital, Beijing, Beijing 100142, China
PRINCIPAL_INVESTIGATORLin Shen, MD
Peking University Cancer Hospital, Beijing, Beijing 100142, China
PRINCIPAL_INVESTIGATORMarkus Mohler, MD
Johannes Gutenberg University Clinic, Germany
Outcome results
None listed