Study Overview
The primary objective of this clinical trial is to evaluate the efficacy and safety of AK112 in combination with chemotherapy as a neoadjuvant treatment for patients with locally advanced, resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma containing signet ring cells.
Key Research Questions
1. Does neoadjuvant treatment with AK112 plus chemotherapy improve the pathological complete response (pCR) rate compared to chemotherapy alone in patients with locally advanced G/GEJ adenocarcinoma with signet ring cells? 2. What are the safety profile and additional efficacy outcomes of AK112 combined with chemotherapy in this patient population?
To answer these questions, the study will compare the combination of AK112 and chemotherapy with chemotherapy alone.
Participant Procedures
Eligible participants will:
1. Receive standard-dose AK112 in combination with chemotherapy every 3 weeks for a total of 4 cycles prior to surgery. 2. Undergo preoperative CT or MRI imaging within 3-4 weeks after the last treatment cycle to assess tumor response and evaluate eligibility for curative resection. 3. If no evidence of disease progression is observed and surgical evaluation is favorable, patients will undergo curative-intent gastrectomy within 6 weeks of completing neoadjuvant therapy (including oral agents, if any). 4. Postoperatively, adjuvant therapy will be administered at the investigator's discretion. Patients will be followed until disease recurrence or metastasis. 5. Attend clinic visits every 6 weeks during the neoadjuvant phase for evaluations and laboratory tests. 6. Maintain a symptom diary throughout the study period. 7. Undergo follow-up assessments every 3 months, starting from the first dose of study medication until 30 days after the last dose or the initiation of a new anti-tumor therapy.
Optional Imaging Substudy FAPI-PET/CT imaging will be explored as an optional diagnostic modality. Participation in this substudy will require separate informed consent and will be conducted under a future protocol amendment (pending IRB approval).
Subjects must voluntarily agree to participate in the clinical trial and sign a written informed consent form (ICF) before undergoing any trial-related procedures.
Male or female subjects aged ≥18 and ≤75 years at the time of signing the informed consent.
Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction with signet ring cell components. Diagnosis of locally advanced disease (based on AJCC 8th edition) must be made within 4 weeks prior to randomization.
Tumor staging: cT3-4a or cN+ (M0) as determined by endoscopic ultrasound and/or contrast-enhanced CT/MRI. Diagnostic laparoscopy may be used as needed. The tumor must be assessed as resectable by the investigator.
Histology other than adenocarcinoma with signet ring cell features, including squamous cell carcinoma, neuroendocrine carcinoma, or other subtypes.
Tumor exhibiting deficient MMR (dMMR) or HER-2 positivity (IHC 3+, or IHC 2+ with FISH-confirmed HER-2 amplification).
Unresectable tumors or subjects unwilling or unable to undergo surgery due to medical, anatomical, or personal reasons.
History of other malignancies within 5 years prior to enrollment, excluding certain cured cancers (e.g., basal cell carcinoma, carcinoma in situ of cervix/breast/prostate/bladder).
Parallel
AK112+oxaliplatin+capecitabine
Drugparticipants will receive standard dose treatment of AK112 combined with oxaliplatin+capecitabine every 3 weeks for 4 cycles before surgery.
oxaliplatin+capecitabine
Drugparticipants will receive standard dose treatment of oxaliplatin+capecitabine every 3 weeks for 4 cycles before surgery
Pathologic Complete Response (pCR)
Absence of viable tumor cells in primary tumor and lymph nodes (Becker TRG 1a)
Objective Response Rate，ORR
Proportion of participants achieving CR or PR per RECIST v1.1 assessed via contrast-enhanced CT/MRI
Disease-Free Survival, DFS
The time between postoperative and disease recurrence or (for any reason) death.
Treatment-Emergent Adverse Events (TEAEs)
Incidence of adverse events graded by CTCAE v6.0
Serious Adverse Events (SAE)
Serious AEs leading to discontinuation
Click on the lead sponsor to view all of their trials.
Peking Union Medical College Hospital
Lead sponsor
Akeso Biopharma Co., Ltd.
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
