Clinical trial NCT05008783: A Study of AK104 in the First-line Treatment of Locally Advanced Unresectable or Metastatic G/GEJ Adenocarcinoma
Official title: A Randomized, Double-blind, Multicenter, Phase III Study Comparing the Efficacy and Safety of AK104 Plus Oxaliplatin and Capecitabine (XELOX) Versus Placebo Plus XELOX as First-line Treatment for Locally Advanced Unresectable or G/GEJ Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Akeso
Sponsor class: INDUSTRY
First posted: 2021-08-17
Enrollment: 610
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: A randomized, Double-blind, Multicenter, phase III Clinical Study of Comparing the Efficacy and Safety of AK104 Plus Oxaliplatin and Capecitabine (XELOX) Versus Placebo Plus XELOX as First-line Treatment for locally advanced Unresectable or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma.


Eligibility criteria: Inclusion Criteria:

* Subjects must meet all of the following inclusion criteria to be enrolled in the study:

  1. Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
  2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
  3. Histopathologically confirmed gastric adenocarcinoma or gastroesophageal junction (GEJ) adenocarcinoma.
  4. Unresectable locally advanced or metastatic gastric adenocarcinoma or GEJ adenocarcinoma.
  5. Subjects have not received prior systemic therapy for locally advanced or metastatic gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction. For subjects who have received prior neoadjuvant/adjuvant chemotherapy or chemoradiotherapy for curative intent, the time between disease progression and last treatment should be at least 6 months.
  6. Subjects have at least one measurable tumor lesion per RECIST v1.1; lesions that received radiotherapy are not selected as target lesions, unless the lesion is the only measurable lesion and has unequivocal progression as judged by imaging, it can be considered as a target lesion.

Exclusion Criteria:

* Subjects who meet any of the following criteria are not eligible to participate in this study:

  1. Subjects with known HER2-positive gastric or GEJ adenocarcinoma.
  2. Histopathology or cytology confirmed other pathological types, such as squamous cell carcinoma, sarcoma, or undifferentiated carcinoma.
  3. Subjects who received palliative local therapy for non-target lesions within 2 weeks prior to the first dose; systemic nonspecific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, etc.) within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 2 weeks prior to the first dose.
  4. Subjects who received any prior treatments targeting the mechanism of tumor immunity.
  5. Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose. If the perforation or fistula has been treated with resection or repair and the disease has recovered or resolved as judged by the Investigator, enrollment may be allowed.
  6. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
  7. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of cervix, carcinoma in situ of breast, localized prostate cancer, etc.
  8. Known active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal disease.
  9. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage (≥ 1/month).
  10. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or autoimmune diseases that may relapse or require scheduled treatment as judged by the Investigator.

Primary outcomes:
measure: Overall Survival (os)
timeFrame: Up to 2 years
Secondary outcomes:
measure: ORR
timeFrame: Up to 2 years
measure: DCR
timeFrame: Up to 2 years
measure: DoR
timeFrame: Up to 2 years
measure: TTR
timeFrame: Up to 2 years
measure: PFS
timeFrame: Up to 2 years
measure: AE
timeFrame: From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first
measure: Observed concentrations of AK104
timeFrame: From first dose of AK104 through the last dose of AK104, about average of 9 months.
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
timeFrame: From first dose of AK104 through 30 days after last dose of AK104
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Shanghai
country: China
facility: Fudan University Cancer Hospital
state: Shanghai
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University Medical College
state: Zhejiang
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jiafu Ji, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, MD
role: PRINCIPAL_INVESTIGATOR
References: