QL1706-SOX vs SOX Alone as Neoadjuvant Therapy for Resectable Diffuse-Type Gastric Cancer

Nanjing Medical University

Status and phase: Not yet enrolling; Phase 2

Conditions: Gastric Cancer Stage III

Treatments: Drug: SOX Chemotherapy; Drug: QL1706 (Iparomlimab/Tuvonralimab)

Study type: Interventional

Funder types: Other

Identifiers

NCT07315035

QILIN-01

Details and patient eligibility

About

The goal of this randomized, open-label, phase II clinical trial is to determine whether adding the PD-1/CTLA-4 bispecific antibody QL1706 to standard SOX chemotherapy increases the pathological complete response rate in adults aged 18-75 years with resectable, locally advanced, diffuse-type, HER2-negative gastric adenocarcinoma (cT3-4aNxM0). Participants will be randomly assigned (1:1) to receive 3-4 neoadjuvant cycles of QL1706 plus SOX or SOX alone every 3 weeks, followed by curative-intent gastrectomy with D2 lymphadenectomy, and will be monitored post-operatively every 3 months for 2 years and every 6 months thereafter for recurrence, survival, and safety.

Enrollment: 74 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Histologically confirmed diffuse-type gastric adenocarcinoma (Lauren classification) with signet-ring cells ≥ 50 % of tumor volume HER2-negative by IHC or ISH per ASCO/CAP guidelines Clinical stage cT3-4aNxM0 (AJCC 8th ed.) on baseline EUS + contrast-enhanced CT/MRI; disease judged resectable by multidisciplinary team No prior gastric surgery, chemotherapy, radiotherapy, or immunotherapy for cancer Age 18-75 years; ECOG performance status 0-1 Adequate organ function (ANC ≥ 1.5 × 10⁹/L, platelet ≥ 100 × 10⁹/L, Hb ≥ 9 g/dL, ALT/AST ≤ 2.5 × ULN, TBIL ≤ 1.5 × ULN, creatinine ≤ 1.5 × ULN and calculated CrCl ≥ 60 mL/min, INR/PT ≤ 1.5 × ULN) within 14 days before randomization Left-ventricular ejection fraction ≥ 50 % by echocardiography; no clinically significant ECG abnormalities Negative serum β-hCG pregnancy test ≤ 7 days of first dose for women of child-bearing potential; agreement to use effective contraception through 6 months post-surgery Life expectancy ≥ 6 months Signed informed consent; able to comply with study procedures and follow-up

Exclusion criteria

Mixed or intestinal Lauren histology; mucinous or hepatoid variants Active gastrointestinal bleeding or endoscopic evidence of major vessel invasion Other malignancy within 5 years (except curatively treated basal-cell carcinoma, cervical carcinoma in situ, or superficial bladder cancer) Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4, or other T-cell co-stimulatory/antagonist agents Autoimmune disease requiring systemic immunosuppression within 2 years (e.g., prednisone > 10 mg/day equivalent) Receipt of live vaccine ≤ 30 days before first dose Known HIV-positive, active hepatitis B (HBsAg+ and HBV-DNA > 200 IU/mL), or hepatitis C infection (HCV RNA positive) Active tuberculosis or history of incompletely treated TB Severe cardiovascular disease: NYHA class ≥ II heart failure, unstable angina, myocardial infarction ≤ 6 months, uncontrolled arrhythmia, or uncontrolled hypertension (systolic > 160 mmHg or diastolic > 100 mmHg) Peripheral neuropathy ≥ grade 2 per NCI-CTCAE v5.0 Pulmonary disease requiring systemic steroids (e.g., ≥ grade 2 pneumonitis) or oxygen therapy Active infection requiring systemic antibiotics, antivirals, or antifungals ≤ 7 days before first dose Known hypersensitivity to oxaliplatin, fluoropyrimidines, or Chinese hamster ovary cell-derived products Pregnancy or lactation Concurrent participation in another interventional clinical trial Any condition that, in the investigator's opinion, would compromise safe completion of protocol therapy or accurate assessment of outcomes

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

QL1706+SOX

Experimental group

Description:

QL1706 (Iparomlimab/Tuvonralimab) 5 mg/kg intravenous infusion on day 1 plus SOX (S-1 40-60 mg orally twice daily days 1-14 and oxaliplatin 130 mg/m² intravenous infusion on day 1) every 3 weeks for 3-4 cycles before curative gastrectomy.

Treatment:

Drug: QL1706 (Iparomlimab/Tuvonralimab)

Drug: SOX Chemotherapy

SOX

Active Comparator group

Description:

S-1 40-60 mg orally twice daily days 1-14 and oxaliplatin 130 mg/m² intravenous infusion on day 1 every 3 weeks for 3-4 cycles before curative-intent gastrectomy.

Treatment:

Drug: SOX Chemotherapy