Iparomlimab and Tuvonralimab (QL1706) plus SOX versus SOX alone for locally advanced gastric or gastroesophageal junction adenocarcinoma

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)

This trial will test whether adding the immunotherapy combination Iparomlimab and Tuvonralimab (QL1706) to standard SOX chemotherapy before and after surgery helps people with locally advanced gastric or gastroesophageal junction adenocarcinoma achieve complete tumor remission.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shandong Provincial Hospital (Government)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Iparomlimab, Tuvonralimab
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT06829797 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, phase II trial comparing neoadjuvant and adjuvant QL1706 combined with SOX chemotherapy versus SOX chemotherapy alone in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma. Eligible patients (T3N+ or T4a, M0) are randomized to receive preoperative treatment, proceed to D2 radical gastrectomy, and then receive adjuvant therapy according to their assigned arm. The primary outcome is the complete pathologic remission rate (pCR); safety and surgical outcomes are also monitored. The trial enrolls adults fit for surgery who have not received prior anti-tumor therapy.

Who should consider this trial

Good fit: Adults aged 18–75 with pathologically confirmed locally advanced (T3N+ or T4a, M0) gastric or gastroesophageal junction adenocarcinoma who are medically fit for D2 resection and have not received prior anti-tumor therapy.

Not a fit: Patients with known HER2-positive tumors, peritoneal metastases or positive peritoneal cytology, unresectable disease, contraindications to surgery, or poor performance status are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could raise complete pathologic remission rates and potentially improve longer-term survival after surgery.

How similar studies have performed: Other trials combining PD-1–axis immunotherapy with chemotherapy in the neoadjuvant setting for gastric cancer have shown promising increases in pCR rates, but the specific QL1706 regimen is relatively novel.

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.

Where this trial is running

Jinan, Shandong

• Shandong Provincial Hospital — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Liang Shang

Conditions Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma