A Multicenter Randomized Controlled Phase II Trial of Iparomlimab and Tuvonralimab (QL1706) Combined with SOX Chemotherapy Versus Chemotherapy Alone in the Treatment of Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

NCT ID: NCT06829797

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-28
• Study Completion Date: 2028-02-29

Brief Summary

To explore the efficacy of Iparomlimab and Tuvonralimab (QL1706) in combination with SOX chemotherapy versus chemotherapy alone for the neoadjuvant treatment of locally-progressed gastric/gastroesophageal union adenocarcinomas by evaluating the complete pathologic remission rate (pCR).

Conditions

Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

QL1706+SOX group

Group Type: EXPERIMENTAL

Neoadjuvant Therapy(QL1706+SOX Chemotherapy)

Intervention Type: DRUG

Preoperative QL1706 combined with SOX regimen (4 cycles) → Radical surgery (D2) → Postoperative QL1706 combined with SOX regimen (4 cycles). QL1706 (50mg/2mL) , at a dose of 5mg/kg, the desired volume of drug is withdrawn and slowly infused into an IV bag of 0.9% NaCl, prepared as a diluent with a final concentration of 1-10mg/mL, mixed, and infused intravenously, Q3W, administered on the first day of each cycle.

Radical surgery (D2)

Intervention Type: PROCEDURE

Surgical treatment is completed within 3-5 weeks after the end of neoadjuvant therapy.

Drug: Adjuvant therapy(QL1706+SOX chemotherapy)

Intervention Type: DRUG

Postoperative adjuvant therapy is 4 cycles of QL1706+SOX chemotherapy.

SOX group

Group Type: ACTIVE_COMPARATOR

Neoadjuvant Therapy(SOX Chemotherapy)

Intervention Type: DRUG

Preoperative SOX regimen (4 cycles) → radical surgery (D2) → postoperative SOX regimen (4 cycles).

Radical surgery (D2)

Intervention Type: PROCEDURE

Surgical treatment is completed within 3-5 weeks after the end of neoadjuvant therapy.

Drug: Adjuvant therapy(SOX chemotherapy)

Intervention Type: DRUG

Postoperative adjuvant therapy is 4 cycles of SOX chemotherapy.

Interventions

Neoadjuvant Therapy(QL1706+SOX Chemotherapy)

Preoperative QL1706 combined with SOX regimen (4 cycles) → Radical surgery (D2) → Postoperative QL1706 combined with SOX regimen (4 cycles). QL1706 (50mg/2mL) , at a dose of 5mg/kg, the desired volume of drug is withdrawn and slowly infused into an IV bag of 0.9% NaCl, prepared as a diluent with a final concentration of 1-10mg/mL, mixed, and infused intravenously, Q3W, administered on the first day of each cycle.

Intervention Type: DRUG

Neoadjuvant Therapy(SOX Chemotherapy)

Preoperative SOX regimen (4 cycles) → radical surgery (D2) → postoperative SOX regimen (4 cycles).

Intervention Type: DRUG

Radical surgery (D2)

Surgical treatment is completed within 3-5 weeks after the end of neoadjuvant therapy.

Intervention Type: PROCEDURE

Drug: Adjuvant therapy(QL1706+SOX chemotherapy)

Postoperative adjuvant therapy is 4 cycles of QL1706+SOX chemotherapy.

Intervention Type: DRUG

Drug: Adjuvant therapy(SOX chemotherapy)

Postoperative adjuvant therapy is 4 cycles of SOX chemotherapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Voluntary participation in the study and signing of informed consent;
• Age ≥18 years and ≤75 years;
• Pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma;
• Clinical staging of T3N+ or T4a any N, M0 (according to AJCC 8th edition staging), with potential radical resection confirmed by CT or MRI;
• Have not received any anti-tumor therapy (e.g., surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy);
• Planned to undergo surgery after completion of neoadjuvant therapy;
• Be able to swallow pills normally;
• ECOG-PS score 0-1;
• Expected survival ≥ 12 months;
• Normal major organ function.

Exclusion Criteria

• Known HER2 positivity;
• Known peritoneal metastases or positive peritoneal cytology (CY1P0) or T4b (according to AJCC 8th edition);
• Presence of unresectable factors including unresectable tumors, contraindications to surgery and refusal of surgery;
• The presence of a pre-existing or concurrent malignancy, with the exception of cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and carcinoma in situ of the breast
• History of gastrointestinal perforation, history of abdominal abscess or recent (within 3 months) occurrence of intestinal obstruction, or concomitant intestinal obstruction as indicated by imaging or clinical signs;
• Patients with abnormal coagulation (International Normalized Ratio (INR) >2.0 or Prothrombin Time (PT) >16s), a bleeding tendency or currently receiving thrombolytic or anticoagulant therapy (prophylactic use of low-dose aspirin and low-molecular-weight heparin is allowed);
• Clinically significant bleeding symptoms or significant bleeding tendency such as gastrointestinal bleeding, gastric ulcer bleeding, and vasculitis within 3 months prior to randomization into groups. Patients with positive fecal occult blood at baseline may be retested, and if the retest remains positive, gastroscopy will be required (except for patients who have had a gastroscopy within 3 months prior to enrollment to rule out this condition);
• Arterial/venous thrombotic events such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis, and pulmonary embolism within 6 months prior to randomization to group;
• A known hereditary or acquired predisposition to bleeding and thrombosis (e.g., hemophilia, coagulation disorders, and thrombocytopenia);
• The presence of active ulcers, unhealed wounds or fractures
• Urinalysis showing urinary protein ≥++, confirmed by 24-hour urine protein quantification >1.0 g;
• Active infections requiring antimicrobial therapy (e.g., antibacterial, antiviral, and antifungal medications);
• Active hepatitis (Hepatitis B reference: HBsAg positive and HBV DNA ≥ 500 IU/mL; Hepatitis C reference: HCV antibody positive and HCV viral copy number > upper limit of normal (ULN));
• Congenital or acquired immunodeficiency (e.g., HIV-infected patients);
• Planned or previous organ or allogeneic bone marrow transplant;
• Current interstitial pneumonia or interstitial lung disease, or a history of interstitial pneumonia or interstitial lung disease requiring hormonal therapy, or other conditions that may interfere with the assessment and management of immune-related pulmonary toxicity, such as pulmonary fibrosis, opportunistic pneumonia (e.g., occlusive bronchiectasis), pneumoconiosis, drug-associated pneumonia, and idiopathic pneumonitis, or active pneumonitis or severe pulmonary impairment as demonstrated by CT at screening; Active tuberculosis;
• Any active autoimmune disease or history of autoimmune disease with potential for relapse;
• Treatment with immunosuppressive drugs or systemic corticosteroids (>10 mg/day of prednisone or equivalent) within 7 days prior to randomization to group;
• Use of a strong CYP3A4 inducer within 2 weeks prior to randomization subgroup or use of a strong CYP3A4 inhibitor within 1 week prior to randomization subgroup
• Oral or intravenous administration of therapeutic antibiotics within 4 weeks prior to randomization to subgroups, except for prophylactic antibiotics administered intravenously for no more than 48 hours
• Known allergy to any study drug or excipient;
• Participation in a clinical study of another drug within 4 weeks prior to randomization to group;
• Being a lactating female.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shandong Provincial Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Li Leping

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Liang Shang

Role: CONTACT

docshang@163.com

+8615866602157

Other Identifiers

NO.2024-1046

Identifier Type: -

Identifier Source: org_study_id