Neoadjuvant Iparomlimab and Tuvonralimab With Nab-P-SOX in Locally Advanced Gastric or Gastroesophageal Junction Cancer

NCT07867392 | Recruiting Phase 2 DMC

• 1 other identifier: 2025247
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, single-arm, phase 2 clinical study testing a new neoadjuvant (pre-surgery) treatment for patients with locally advanced gastric cancer or gastroesophageal junction (GEJ) cancer. The treatment combines two parts: (1) a novel bispecific immunotherapy drug, iparomlimab and tuvonralimab (Qibain®) , which helps the immune system attack cancer cells by blocking the PD-1 and CTLA-4 pathways; and (2) a standard chemotherapy regimen called nab-P-SOX, made up of nab-paclitaxel, oxaliplatin, and S-1. About 28 adults (aged 18-75) with previously untreated, HER2-negative, locally advanced gastric or GEJ adenocarcinoma (clinical stage cT3-4aN+M0) will receive this combination before their planned surgery. The main goal is to see how well the tumor shrinks, measured by the objective response rate (RECIST v1.1). Secondary goals include the rate of complete response in the removed tumor tissue (pathological complete response), how often the cancer is removed with clear margins (R0 resection), survival outcomes, and the safety of the treatment. All participants will be closely followed to track both benefits and side effects. The study is sponsored by Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, with funding and the study drug provided by Qilu Pharmaceutical Co., Ltd.

Conditions

Gastric Adenocarcinoma

Keywords

Gastroesophageal Junction Cancer; Neoadjuvant Therapy; Iparomlimab and Tuvonralimab; PD-1/CTLA-4 Bispecific Antibody; Nab-paclitaxel; Oxaliplatin; S-1

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Baseline through pre-surgical restaging (after 4 neoadjuvant cycles of 21 days each; approximately 12 weeks from first dose)

Secondary Outcomes (1)

• Disease Control Rate (DCR), Defined as Complete Response + Partial Response + Stable Disease per RECIST v1.1

  Baseline through pre-surgical restaging (after 4 neoadjuvant cycles of 21 days each; approximately 12 weeks from first dose)

Study Arms (1)

Iparomlimab and Tuvonralimab Plus nab-P-SOX as Neoadjuvant Therapy

EXPERIMENTAL

All participants in this single experimental arm receive neoadjuvant therapy with iparomlimab and tuvonralimab (QL1706; trade name Qibain®) in combination with the nab-P-SOX chemotherapy regimen, administered as 4 cycles on a 21-day schedule, followed by curative-intent surgery. On Day 1 of each 21-day cycle: Iparomlimab and tuvonralimab: 5 mg/kg by intravenous (IV) infusion; Nab-paclitaxel (albumin-bound paclitaxel): 150 mg/m² IV; Oxaliplatin: 130 mg/m² IV; S-1 (tegafur/gimeracil/oteracil): oral, twice daily on Days 1-14, with dose by body-surface area (\<1.25 m²: 40 mg/dose; 1.25-1.5 m²: 50 mg/dose; \>1.5 m²: 60 mg/dose). Curative-intent surgery is performed within 4 weeks after the last neoadjuvant cycle. Postoperative adjuvant treatment is left to the investigator's discretion. Dose interruptions, reductions, or permanent discontinuation follow the protocol's toxicity management rules (NCI CTCAE v5.0); dose is not re-escalated after reduction.

Drug: Iparomlimab and Tuvonralimab (QL1706); Drug: nab-P-SOX（nab-paclitaxel, oxaliplatin, S-1）

Interventions

Iparomlimab and Tuvonralimab (QL1706) DRUG

A recombined anti-PD-1/CTLA-4 bispecific antibody (development code QL1706) administered at a fixed dose of 5 mg/kg by intravenous infusion on Day 1 of each 21-day cycle for 4 cycles. This agent is distinguished from conventional immunotherapy by concurrently targeting both PD-1 and CTLA-4 inhibitory pathways within a single molecule, in contrast to sequential or separate use of a PD-1 inhibitor plus ipilimumab (CTLA-4 inhibitor). It is explored here in the neoadjuvant (pre-surgical) window rather than in the metastatic or adjuvant setting.

Iparomlimab and Tuvonralimab Plus nab-P-SOX as Neoadjuvant Therapy

nab-P-SOX（nab-paclitaxel, oxaliplatin, S-1） DRUG

A triplet chemotherapy backbone given on Day 1 of each 21-day cycle for 4 cycles: nab-paclitaxel 150 mg/m² IV, oxaliplatin 130 mg/m² IV, plus S-1 (tegafur/gimeracil/oteracil) orally 40-60 mg twice daily on Days 1-14 (dose by BSA). This regimen is distinguished from the more common SOX (S-1 + oxaliplatin) or mFOLFOX by the addition of albumin-bound paclitaxel to form a three-drug triplet, and by the inclusion of S-1, an oral fluoropyrimidine more commonly used in Asian gastric-cancer populations.

Iparomlimab and Tuvonralimab Plus nab-P-SOX as Neoadjuvant Therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 18-75 years. 2. Histologically confirmed gastric or gastroesophageal junction (GEJ) adenocarcinoma, with clinical stage cT3-4aN+M0.
• \. Resectable disease, as determined by the surgical investigator. 4. No prior radiotherapy, chemotherapy, or other systemic antitumor therapy. 5. HER-2 negative. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 7. Life expectancy \> 6 months. 8. Adequate organ function, defined as: hemoglobin (Hb) ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 100 × 10⁹/L, serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN), alanine/aspartate aminotransferase (ALT/AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN, amylase/lipase \< 1.5 × ULN, international normalized ratio (INR)/activated partial thromboplastin time (APTT) ≤ 1.5 × ULN, urine protein \< 2+, left ventricular ejection fraction (LVEF) ≥ 50%, etc.
• \. Women of childbearing potential must be non-pregnant, non-lactating, and agree to use adequate contraception.
• \. Voluntary provision of written informed consent, with good treatment compliance anticipated.

You may not qualify if:

• \. Known allergy or hypersensitivity to the investigational drug(s) or any of their excipients.
• \. History of other prior antitumor therapy. 3. Therapeutic full-dose anticoagulation or thrombolysis within 10 days prior to the first dose.
• \. Requirement for systemic corticosteroids or immunosuppressive therapy within 2 weeks prior to the first dose.
• \. Active autoimmune disease, or an autoimmune disease with a high risk of relapse upon immunosuppression.
• \. Within 6 months: gastrointestinal perforation, fistula, or obstruction; Crohn's disease or ulcerative colitis; or extensive intestinal resection.
• \. Symptomatic and uncontrolled brain or leptomeningeal metastases. 8. History of interstitial lung disease/pneumonitis, or pulmonary hypertension. 9. History of organ transplantation. 10. Uncontrolled hypertension (\>150/100 mmHg), diabetes mellitus, or cardiac arrhythmia.
• \. Arterial or venous thrombotic/embolic event within 6 months. 12. Within 12 months: myocardial infarction, unstable angina, or New York Heart Association (NYHA) class III/IV heart failure.
• \. Drainage of ascites, pleural effusion, or pericardial effusion within 4 weeks prior to enrollment.
• \. Non-healing wound, active ulcer, or untreated fracture. 15. Other active malignancy (except cured basal/squamous cell skin carcinoma or in situ carcinoma).
• \. Active HIV, HBV, or HCV infection. 17. Major surgery within 4 weeks prior to the first dose. 18. Any other condition that, in the investigator's judgment, renders the patient unsuitable for study participation.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Shanghai Jiaotong Univeristy School of Medicine Affiliated Ruijin Hospital

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Interventions

Oxaliplatin; S 1 (combination)

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Hao Li

  Ruijin Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Li

CONTACT

86-21-64370045; lh11001@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, prospective, open-label phase 2 study conducted under a single-group assignment model. All eligible participants receive the identical neoadjuvant combination (iparomlimab and tuvonralimab plus nab-P-SOX); there is no randomization, no placebo, and no parallel comparator arm. Each patient serves as their own control through paired assessment of baseline tumor staging and post-neoadjuvant surgical pathology (a within-subject, before-and-after design). No stratification, blocking, or alternate treatment allocation beyond the single experimental cohort is applied.

Study Record Dates

• First Submitted: October 5, 2026
• First Posted: October 9, 2026
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): February 1, 2030
• Last Updated: October 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)