Gastric Adenocarcinoma
Conditions
Keywords
Gastroesophageal Junction Cancer, Neoadjuvant Therapy, Iparomlimab and Tuvonralimab, PD-1/CTLA-4 Bispecific Antibody, Nab-paclitaxel, Oxaliplatin, S-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.
Detailed description
Background and Rationale Gastric and gastroesophageal junction (GEJ) adenocarcinoma remains a leading cause of cancer mortality, and patients with locally advanced disease (cT3-4aN+M0) face a high risk of recurrence even after curative-intent surgery. Neoadjuvant systemic therapy is the established strategy to improve R0 resection rates and long-term outcomes. Although PD-1/PD-L1 immune checkpoint inhibitors have entered the treatment landscape of advanced gastric cancer, the incremental value of CTLA-4 blockade in the perioperative setting remains an active question. Iparomlimab and tuvonralimab (QL1706; trade name Qibain®) is a bispecific antibody that concurrently engages PD-1 and CTLA-4, potentially enhancing T-cell activation within the tumor microenvironment. Preclinical and early clinical evidence suggests that a chemotherapy backbone can potentiate immunotherapy activity. This study investigates whether neoadjuvant iparomlimab and tuvonralimab combined with the nab-P-SOX regimen (nab-paclitaxel, oxaliplatin, and S-1) improves tumor response and resectability in locally advanced, HER2-negative gastric/GEJ adenocarcinoma. Study Design and Procedures This is a prospective, single-center, single-arm, open-label, phase 2 study. Eligible participants (see Eligibility) will receive neoadjuvant iparomlimab and tuvonralimab in combination with P-SOX for a protocol-defined number of cycles, followed by restaging and curative-intent surgery with standardized pathological assessment of the surgical specimen. Postoperative management follows institutional practice. Participants are followed through scheduled visits for efficacy and safety; tumor response is evaluated by imaging and surgical pathology, and adverse events are graded per CTCAE (full intervention details, dosing, and schedule are provided in the Arms and Interventions section). Objectives The primary objective is to evaluate the antitumor activity of the neoadjuvant regimen. Secondary objectives assess pathological response, resectability, survival, and safety. Formal endpoint definitions, assessment time points, and the statistical analysis plan-including sample size justification and methods for handling the single-arm design-are detailed in the Outcomes and statistical sections and are not repeated here. Exploratory analyses will examine candidate biomarkers potentially associated with treatment response.
Interventions
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.
DRUGnab-P-SOX（nab-paclitaxel, oxaliplatin, S-1）
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.
Sponsors
Ruijin Hospital
Qilu Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years * Histologically confirmed gastric or gastroesophageal junction adenocarcinoma, clinical stage cT3-4aN+M0 * Resectable disease, as determined by the surgical investigator * No prior radiotherapy, chemotherapy, or other systemic antitumor therapy * HER-2 negative * ECOG performance status 0-1 * Life expectancy greater than 6 months * Adequate organ function: hemoglobin \>= 90 g/L; absolute neutrophil count \>= 1.5 x 10\^9/L; platelet count \>= 100 x 10\^9/L; serum creatinine \<= 1.5 x ULN; ALT/AST \<= 2.5 x ULN; total bilirubin \<= 1.5 x ULN; amylase/lipase \< 1.5 x ULN; INR/APTT \<= 1.5 x ULN; urine protein \< 2+; LVEF \>= 50% * Women of childbearing potential must be non-pregnant, non-lactating, and agree to use adequate contraception * Provision of written informed consent and anticipated good compliance
Exclusion criteria
* Known allergy or hypersensitivity to the investigational drug(s) or excipients * History of other prior antitumor therapy * Therapeutic full-dose anticoagulation or thrombolysis within 10 days prior to first dose * Requirement for systemic corticosteroids or immunosuppressive therapy within 2 weeks prior to first dose * Active autoimmune disease or autoimmune disease with high risk of relapse * 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 * History of interstitial lung disease/pneumonitis or pulmonary hypertension * History of organ transplantation * Uncontrolled hypertension (\>150/100 mmHg), diabetes mellitus, or cardiac arrhythmia * Arterial or venous thrombotic/embolic event within 6 months * Within 12 months: myocardial infarction, unstable angina, or 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 * Other active malignancy * Active HIV, HBV, or HCV infection * Major surgery within 4 weeks prior to first dose * Any condition that, in the investigator's judgment renders the patient unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
Countries
China
Contacts
CONTACTHao Li
PRINCIPAL_INVESTIGATORHao Li
Ruijin Hospital
Outcome results
None listed