The goal of this Phase II clinical trial is to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab (QL1706) combined with SOX chemotherapy (S-1 plus Oxaliplatin) in patients with previously untreated advanced or metastatic gastric cancer or gastroesophageal junction cancer. The main questions it aims to answer are: 1、What is the objective response rate (ORR) of the combination of QL1706 and SOX chemotherapy? 2、What are the safety and tolerability of this combination therapy? Participants will: 1. Receive Iparomlimab and Tuvonralimab (QL1706) via intravenous infusion every 3 weeks. 2. Receive SOX chemotherapy (Oxaliplatin via intravenous infusion on Day 1 and S-1 orally twice daily for 14 days) every 3 weeks for up to 6 cycles. 3. Continue maintenance therapy with QL1706 combined with S-1 after 6 cycles until disease progression or unacceptable toxicity. 4. Undergo tumor imaging assessments (CT or MRI) every 6 weeks for the first 24 weeks, and then every 9 weeks thereafter to monitor the disease.
Study Design: This is a prospective, single-center, single-arm, exploratory Phase II clinical study designed to evaluate the efficacy and safety of Iparomlimab and Tuvonralimab (QL1706) combined with SOX chemotherapy (S-1 and Oxaliplatin) as a first-line treatment for patients with advanced or metastatic gastric or gastroesophageal junction (GEJ) cancer. The study aims to enroll approximately 32 eligible participants. Intervention and Treatment Regimen: Eligible participants will undergo a screening period of up to 3 weeks. Upon enrollment, subjects will receive the combination therapy in 3-week cycles as follows: Induction Phase (Cycles 1-6): Iparomlimab and Tuvonralimab (QL1706): Administered intravenously at a fixed dose of 5 mg/kg on Day 1 of each cycle. Oxaliplatin: Administered intravenously at a dose of 130 mg/m² on Day 1 of each cycle. S-1 (Tegafur, Gimeracil, Oteracil): Administered orally twice daily (after breakfast and dinner) on Days 1-14, followed by a 7-day rest period. The dose is calculated based on body surface area (BSA): 40 mg/dose for BSA ≤1.25 m²; 50 mg/dose for BSA 1.25-1.5 m²; and 60 mg/dose for BSA \>1.5 m². Maintenance Phase (Cycle 7 onwards): After completing 6 cycles of the combination therapy, patients without disease progression or intolerable toxicity will continue with maintenance therapy consisting of QL1706 (5 mg/kg IV q3w) combined with S-1 (oral, same schedule) until disease progression, death, intolerable toxicity, or withdrawal of consent. Note: Oxaliplatin is discontinued in the maintenance phase. Assessments: Efficacy is assessed using tumor imaging (CT/MRI) according to RECIST v1.1 criteria. Tumor assessments are performed every 6 weeks for the first 24 weeks and every 9 weeks thereafter. The primary endpoint is the Objective Response Rate (ORR). Secondary endpoints include Disease Control Rate (DCR), Progression-Free Survival (PFS), Overall Survival (OS), and 1-year PFS/OS rates. Safety is monitored throughout the study via adverse event reporting (NCI-CTCAE v5.0), laboratory tests, and physical examinations. Follow-up: After treatment discontinuation, patients will enter a safety follow-up period (90 days post-last dose) and a survival follow-up period, where survival status and subsequent anti-tumor therapies will be collected every 2 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
Administered via intravenous (IV) infusion at a dose of 5 mg/kg on Day 1 of each 3-week cycle.
Oxaliplatin: 130mg/m2, iv.gtt, single infusion, 21 days as a cycle, Day 1. Tigio: 40mg (body surface area(BSA)\<1.25m2), 50mg (BSA≥1.25m2, and BAS\<1.5m2), 60mg (BSA ≥1.5m2), p.o, bid, 21 days as a cycle, Day 1-14.
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGObjective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Time frame: From baseline until disease progression or loss of clinical benefit, assessed every 6 weeks for the first 24 weeks, then every 9 weeks, up to approximately 2 years.
Disease Control Rate (DCR)
DCR is defined as the percentage of participants whose Best Overall Response (BOR) is confirmed as Complete Response (CR), Partial Response (PR), or Stable Disease (SD), as assessed by the investigator according to RECIST v1.1.
Time frame: From baseline until disease progression or loss of clinical benefit, assessed every 6 weeks for the first 24 weeks, then every 9 weeks, up to approximately 2 years.
Progression-Free Survival (PFS)
PFS is defined as the time from the date of enrollment to the date of the first documented disease progression (according to RECIST v1.1) or death from any cause, whichever occurs first.
Time frame: From enrollment to the date of first documented progression or death, assessed up to approximately 2 years.
Overall Survival (OS)
OS is defined as the time from the date of enrollment to the date of death due to any cause.
Time frame: From enrollment to the date of death, assessed up to approximately 2 years.
1-Year Progression-Free Survival (PFS) Rate
The proportion of participants who are alive and free of disease progression at 1 year after enrollment.
Time frame: At 1 year after enrollment.
1-Year Overall Survival (OS) Rate
The proportion of participants who are alive at 1 year after enrollment.
Time frame: At 1 year after enrollment.
Incidence and Severity of Adverse Events (AEs)
Safety and tolerability will be evaluated by monitoring the incidence and severity of Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment-Related Adverse Events (TRAEs), and Immune-Related Adverse Events (irAEs). Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Time frame: From the time of informed consent through 90 days after the last dose of study drug.
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