Gastric Cancer (GC), Gastroesophageal Junction Cancer, Advanced Gastric Cancer, Metastatic Gastric Cancer
Conditions
Keywords
Iparomlimab and Tuvonralimab, QL1706, Advanced or Metastatic Gastric Cancer, PD-1/CTLA-4 Bispecific Antibody, Immunotherapy, Chemotherapy Combination, Gastric Cancer
Brief summary
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.
Detailed description
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.
Interventions
Administered via intravenous (IV) infusion at a dose of 5 mg/kg on Day 1 of each 3-week cycle.
DRUGSOX Chemotherapy
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.
Sponsors
Beijing Friendship Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily participate in the clinical study; fully understand and are informed about the study and sign the Informed Consent Form (ICF); willing to follow and able to complete all trial procedures. * Age 18-80 years, gender is not limited. * Patients with locally advanced unresectable, recurrent unresectable, or metastatic gastric cancer (GC) or gastroesophageal junction cancer (GEJC) confirmed by imaging and other examinations, and histopathologically confirmed as adenocarcinoma. * Provide a report confirming HER2 overexpression or amplification negativity; defined as IHC 0/1+, or IHC 2+ with FISH/ISH negative. * No prior systemic therapy for advanced or metastatic GC/GEJC (including anti-HER-2 therapy). Patients who have received adjuvant or neoadjuvant therapy (including chemotherapy, radiotherapy, or chemoradiotherapy) for GC/GEJC are eligible if the time to first recurrence or disease progression is greater than 6 months from the end of the last treatment. Prior use of anti-tumor Traditional Chinese Medicine preparations is allowed but must be discontinued at least 2 weeks before enrollment. * ECOG performance status score of 0 or 1. * Must have at least one measurable lesion according to RECIST v1.1 definitions. * All acute toxicities caused by prior anti-tumor therapy or surgery must have resolved to Grade 0-1 (according to NCI CTCAE v5.0) or to the level specified in the inclusion/
Exclusion criteria
. Alopecia, fatigue, and hearing loss, or other toxicities considered by the investigator not to pose a safety risk to the subject, are excluded. * Adequate organ function (laboratory tests within 7 days prior to treatment): * Hematology (No blood transfusion, G-CSF use, or drug correction within 14 days prior to screening): * White blood cell count (WBC) ≥ 3,000/mm³ (3.0 × 10⁹/L); * Absolute neutrophil count (ANC) ≥ 1,500/mm³ (1.5 × 10⁹/L); * Platelet count (PLT) ≥ 100,000/mm³ (100 × 10⁹/L); * Hemoglobin (Hb) ≥ 9.0 g/dL (90 g/L). * Biochemistry (No albumin transfusion within 14 days prior to screening): * Albumin ≥ 3.0 g/dL (30 g/L); * Creatinine ≤ 1.5 × Upper Limit of Normal (ULN) or Creatinine Clearance ≥ 50 ml/min (calculated using the Cockcroft-Gault formula); * Total Bilirubin (BIL) ≤ 1.5 × ULN; * Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels ≤ 2.5 × ULN; for patients with liver metastases, ≤ 5 × ULN. * Coagulation: International Normalized Ratio (INR) ≤ 1.5, Prothrombin Time (PT), and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN. * Urine: Urine protein \< 2+; if urine protein is ≥ 2+, 24-hour urine protein quantification must be ≤ 1g. * Life expectancy ≥ 3 months. * Women of childbearing potential must undergo a serum or urine pregnancy test within 7 days before starting treatment, with a negative result, and must not be lactating. All enrolled patients must use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From enrollment to the date of first documented progression or death, assessed up to approximately 2 years. | 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. |
| Overall Survival (OS) | From enrollment to the date of death, assessed up to approximately 2 years. | OS is defined as the time from the date of enrollment to the date of death due to any cause. |
| Disease Control Rate (DCR) | 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. | 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. |
| 1-Year Overall Survival (OS) Rate | At 1 year after enrollment. | The proportion of participants who are alive at 1 year after enrollment. |
| Incidence and Severity of Adverse Events (AEs) | From the time of informed consent through 90 days after the last dose of study drug. | 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. |
| 1-Year Progression-Free Survival (PFS) Rate | At 1 year after enrollment. | The proportion of participants who are alive and free of disease progression at 1 year after enrollment. |
Countries
China
Contacts
Primary ContactWei Deng, MD
Outcome results
None listed