Iparomlimab Tolvorlimab as Neoadjuvant Immunotherapy for Locally Advanced Gastric Adenocarcinoma With Microsatellite Instability/Mismatch Repair Deficiency

NCT07595523 | Not Yet Recruiting Phase 2

• 1 other identifier: LGH2026123
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Study Background

1. 1.Clinical Rationale and Unmet Medical Need Gastric cancer is the 5th most common malignancy and the 3rd leading cause of cancer death worldwide. China accounts for \>40% of global new cases, with nearly 90% of patients diagnosed at locally advanced stages and a 5-year overall survival (OS) rate of only 10%-49%. East Asia alone represents 58% of the global gastric cancer burden, with China reporting approximately 400,000 new cases and high mortality annually.
2. 2.Immunotherapy Advances in dMMR/MSI-H Gastric Cancer Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have revolutionized the treatment of dMMR/MSI-H tumors by restoring anti-tumor immune responses. The phase II KEYNOTE-585 study (NCT03221426), the largest trial of neoadjuvant PD-1 monotherapy in this population, demonstrated a pathological complete response (pCR) rate of 32.8%, objective response rate (ORR) of 65.3%, and 3-year progression-free survival (PFS) rate of 78.5%-significantly superior to traditional chemotherapy (pCR 12.3%, 3-year PFS 52.1%). A phase II study of sintilimab monotherapy reported a pCR rate of 34.2%, major pathological response (MPR) rate of 52.2%, and grade ≥3 treatment-related adverse event (TRAE) rate of only 8.7%.
3. 3.Study Agent: Apalimab/Tovorilimab (QL1706) Apalimab/Tovorilimab (QL1706) is a first-in-class bifunctional combination antibody developed using the MabPair® technology platform. It comprises anti-PD-1 antibody (apalimab) and anti-CTLA-4 antibody (tovorilimab) in a 2:1 molar ratio, simultaneously blocking both immune checkpoint pathways for synergistic anti-tumor activity.
4. 4.Study Objectives and Significance This is a prospective, single-arm, single-center phase II clinical trial designed to evaluate the efficacy and safety of QL1706 as neoadjuvant therapy in patients with dMMR/MSI-H locally advanced gastric adenocarcinoma. The primary objective is to assess the pCR rate, with secondary objectives including ORR, MPR rate, R0 resection rate, PFS, OS, and safety profile.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  The proportion of subjects with no residual viable tumor cells identified under microscopic examination of the surgically resected specimen, and no evidence of lymph node metastasis (ypT0N0).

  Assessed at the time of radical gastrectomy, which is performed 4-8 weeks after completion of neoadjuvant therapy.

Secondary Outcomes (6)

• Major Pathological Response (MPR) Rate

  Assessed at the time of radical gastrectomy (4-8 weeks after completion of neoadjuvant therapy)

• Objective Response Rate (ORR)

  Assessed within 1 week before radical gastrectomy (4-8 weeks after completion of neoadjuvant therapy)

• 3-Year Event-Free Survival (EFS) Rate

  From study enrollment to 3 years post-enrollment, assessed every 6 months

• 3-Year Disease-Free Survival (DFS) Rate

  From radical gastrectomy to 3 years post-surgery, assessed every 6 months

• Overall Survival (OS)

  From study enrollment to study completion (3 years), assessed every 6 months

Study Arms (1)

Iparomlimab/Tuvonralimab (QL1706) Neoadjuvant and Adjuvant Immunotherapy

EXPERIMENTAL

All eligible patients will receive a fixed perioperative treatment regimen consisting of neoadjuvant immunotherapy, radical surgery, and adjuvant immunotherapy: Neoadjuvant Phase: Iparomlimab/tovorilimab (QL1706) 5 mg/kg administered as an intravenous infusion on Day 1 of each 3-week cycle, for a total of 4 cycles. Surgical Phase: Radical D2 gastrectomy will be performed 4-8 weeks after the last dose of neoadjuvant therapy, according to standard surgical practice for gastric cancer. Adjuvant Phase: Patients who recover adequately from surgery will receive an additional 4 cycles of iparomlimab/tovorilimab (QL1706) 5 mg/kg intravenously every 3 weeks, starting 4-6 weeks postoperatively. Dosing may be delayed or adjusted based on treatment-related adverse events graded according to the NCI-CTCAE version 5.0 criteria. Patients will be monitored for safety throughout the treatment period and followed for long-term survival outcomes.

Drug: Iparomlimab/Tuvonralimab (QL1706)

Interventions

Iparomlimab/Tuvonralimab (QL1706) DRUG

In this study, QL1706 is administered as a single-agent immunotherapy in the perioperative setting for patients with locally advanced dMMR/MSI-H gastric or gastroesophageal junction adenocarcinoma. The intervention consists of: Neoadjuvant phase: 5 mg/kg intravenous infusion on Day 1 of each 3-week cycle, for a total of 4 cycles Adjuvant phase: 5 mg/kg intravenous infusion on Day 1 of each 3-week cycle, for an additional 4 cycles, starting 4-6 weeks after radical D2 gastrectomy

Iparomlimab/Tuvonralimab (QL1706) Neoadjuvant and Adjuvant Immunotherapy

Eligibility Criteria

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

You may qualify if:

• The subject voluntarily enrolls in this study, is able to provide signed informed consent, and has good compliance.
• Aged 18 to 75 years (at the time of signing informed consent), male or female.
• Histologically confirmed gastric adenocarcinoma, clinically staged as Stage II-III (locally advanced) per AJCC 8th edition based on endoscopic ultrasound or contrast-enhanced CT/MRI scan. The subject agrees to undergo radical resection, and the lesion is assessed as resectable by the investigator. No prior systemic therapy for the current disease, including anti-tumor chemotherapy, radiotherapy, or immunotherapy.
• Tumor biopsy demonstrates dMMR status and concurrently meets the criteria for MSI-H.
• ECOG performance status score of 0 to 1.
• Expected survival ≥ 6 months.
• Adequate major organ function, meeting the following criteria: a) Routine blood test (without blood transfusion or hematopoietic stimulating agents within 14 days): Hemoglobin (Hb) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L; Platelets (PLT) ≥ 100 × 10⁹/L; b) Blood biochemistry: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN; Total Bilirubin (TBIL) ≤ 1.5 × ULN; Serum Creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min; Coagulation function: Activated Partial Thromboplastin Time (APTT), International Normalized Ratio (INR), Prothrombin Time (PT) ≤ 1.5 × ULN; c) Doppler echocardiography: Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• Subjects of reproductive potential must use an effective contraceptive method during the study and for 120 days after study completion. Female subjects must have a negative serum pregnancy test within 7 days prior to enrollment and must not be breastfeeding.

You may not qualify if:

• History of other malignant diseases other than gastric cancer diagnosed within 5 years prior to the first dose (excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, radically resected carcinoma in situ, and papillary thyroid carcinoma curable by local treatment).
• Currently participating in an interventional clinical study, or having received other investigational medicinal products or investigational device therapy within 4 weeks prior to the first dose.
• Received systemic therapy with Chinese patent medicine with anti-tumor indications or immunomodulatory agents (including thymosin, interferon, interleukin, excluding local use for pleural effusion control) within 2 weeks prior to the first dose.
• History of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is not considered systemic therapy.
• Receiving systemic corticosteroid therapy (excluding nasal, inhaled, or other topical corticosteroids) or any other form of immunosuppressive therapy within 7 days prior to the first dose.Note: Physiological doses of corticosteroids (≤10 mg/day prednisone or equivalent) are permitted.
• History of allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• Known hypersensitivity to any study drug used in this study.
• Peripheral neuropathy ≥ Grade 2.
• Known history of human immunodeficiency virus (HIV) infection (i.e., positive HIV 1/2 antibody).
• Received live vaccine within 30 days prior to the first dose (Day 1 of Cycle 1). Note: Inactivated seasonal influenza vaccine by injection within 30 days prior to the first dose is permitted; however, live attenuated influenza vaccine administered intranasally is not permitted.
• Pregnant or lactating female subjects.
• Presence of any severe or uncontrolled systemic disease, such as: a) Significant and symptomatic uncontrolled abnormalities in cardiac rhythm, conduction, or morphology on resting ECG; b) Unstable angina pectoris, congestive heart failure, chronic heart failure with NYHA class ≥ 2; c) Any arterial thrombosis, embolism, or ischemia within 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack; d) History of non-infectious pneumonitis requiring corticosteroid therapy within 1 year prior to the first dose, or current clinically active interstitial lung disease; e) Active pulmonary tuberculosis; f) Active or uncontrolled infection requiring systemic therapy; g) Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction; h) Liver disease such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; i) Urinalysis showing urine protein ≥ ++ and confirmed 24-hour urine protein \> 1.0 g; j) Mental disorders that prevent cooperation with study treatment.
• Presence of medical history, abnormal findings, or laboratory abnormalities that may interfere with study results or prevent the subject from completing the study; or any other conditions deemed by the investigator to be inappropriate for enrollment or to pose other potential risks.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Zhaode Bu, Ph.D

CONTACT

0086-10-88196970; dr.guohaiyang@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Ward 2, GI Cancer Center, Peking University Cancer Hospital& Institute

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share