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 (STAR-03)

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(STAR-03)

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).

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: Neoadjuvant Therapy(QL1706+SOX Chemotherapy); Procedure: Radical surgery (D2); Drug: Drug: Adjuvant therapy(QL1706+SOX chemotherapy); Drug: Neoadjuvant Therapy(SOX Chemotherapy); Drug: Drug: Adjuvant therapy(SOX chemotherapy)

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liang Shang; Phone Number: +8615866602157; Email: docshang@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250021
      • Recruiting
      • Shandong Provincial Hospital
      • Contact: Liang Shang, doctor; Phone Number: 15866602157; Email: shangliang@sdfmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QL1706+SOX group	Drug: 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.; Procedure: Radical surgery (D2); Surgical treatment is completed within 3-5 weeks after the end of neoadjuvant therapy.; Drug: Drug: Adjuvant therapy(QL1706+SOX chemotherapy); Postoperative adjuvant therapy is 4 cycles of QL1706+SOX chemotherapy.
Active Comparator: SOX group	Procedure: Radical surgery (D2); Surgical treatment is completed within 3-5 weeks after the end of neoadjuvant therapy.; Drug: Neoadjuvant Therapy(SOX Chemotherapy); Preoperative SOX regimen (4 cycles) → radical surgery (D2) → postoperative SOX regimen (4 cycles).; Drug: Drug: Adjuvant therapy(SOX chemotherapy); Postoperative adjuvant therapy is 4 cycles of SOX chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR)	Pathological complete response was defined as pT0N0M0	From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 14-16 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	From the beginning of the study to the time of the first occurrence of any of the following events, disease progression beyond surgical treatment, local or distant recurrence, death from any cause, etc.	From date of neoadjuvant therapy until the date of the first occurrence of the above events, assessed up to 60 months.
Overall survival (OS)	From study inception to patient death from any cause.	From the date of diagnosis to the date of death, assessed up to 60 months.
Major pathological response rate (MPR)	The percentage of surviving tumor cells in the tumor bed after neoadjuvant therapy was ≤10%.	From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 14-16 weeks.
R0 resection rate	The proportion of patients who completed R0 resection in the total enrolled patients.	From date of neoadjuvant therapy until the date of postoperative pathological assessment, assessed up to 14-16 weeks.
Disease-free survival (DFS)	The time from randomization until disease recurrence or death due to disease progression.	From date of neoadjuvant therapy until the date of the disease recurrence or death due to disease progression, assessed up to 60 months.
Surgical safety	The occurrence of postoperative complications including surgical site infection, anastomotic leakage, gastrointestinal bleeding, incisional dehiscence, adhesive bowel obstruction, biliary and celiac fistulae, and unexplained fever (≥37.5°C).	From date of neoadjuvant therapy until the date of 30 days post-surgery, assessed up to 17-19 weeks.
Adverse Events	Based on NCI-CTCAE (version 5.0) adverse events (AEs): including type, incidence, grading, severity, duration, and relevance to the study drug	From the date of neoadjuvant therapy to the completion of postoperative adjuvant therapy, up to 24 months.
Drug tolerance	The proportion of dose interruptions, dose reductions, and discontinuations due to drug-related toxicity during the study period.	From the date of neoadjuvant therapy to the completion of postoperative adjuvant therapy, up to 24-28 weeks.
Prognostic Biomarkers	Biomarkers of interest include PD-L1 expression (assessed by IHC), microsatellite instability (MSI) status (determined by PCR-based testing), tumor mutation burden (TMB) (evaluated using next-generation sequencing), and circulating tumor DNA (ctDNA) levels (quantified via liquid biopsy). The correlation between these biomarkers and treatment efficacy, including progression-free survival (PFS) and overall survival (OS), will be analyzed.	From the date of neoadjuvant therapy initiation until the end of postoperative follow-up, up to 24 months.

Collaborators and Investigators

• Sponsor: Shandong Provincial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2025
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Esophageal Neoplasms; Adenocarcinoma
• Other Study ID Numbers: NO.2024-1046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No