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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
66
participants will receive standard dose treatment of AK112 combined with oxaliplatin+capecitabine every 3 weeks for 4 cycles before surgery.
participants will receive standard dose treatment of oxaliplatin+capecitabine every 3 weeks for 4 cycles before surgery
Department of Cancer Medical Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College
Beijing, China
Pathologic Complete Response (pCR)
Absence of viable tumor cells in primary tumor and lymph nodes (Becker TRG 1a)
Time frame: At surgery
Objective Response Rate,ORR
Proportion of participants achieving CR or PR per RECIST v1.1 assessed via contrast-enhanced CT/MRI
Time frame: After 2 neoadjuvant cycles (6 weeks), and 4 neoadjuvant cycles(12 weeks)
Disease-Free Survival, DFS
The time between postoperative and disease recurrence or (for any reason) death.
Time frame: Assessed every 12 weeks via CT/MRI up to 60 months from postoperative.
Treatment-Emergent Adverse Events (TEAEs)
Incidence of adverse events graded by CTCAE v6.0
Time frame: First dose to 90 days post-surgery
Serious Adverse Events (SAE)
Serious AEs leading to discontinuation
Time frame: First dose to 90 days post-surgery
R0 Resection Rate
Percentage of participants achieving microscopically margin-negative resection
Time frame: At surgery
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