NCT07053150

A Prospective, Open-label, Exploratory Basket Trial to Evaluate the Efficacy and Safety of Sintilimab Combined With Pyrotinib ± Chemotherapy in Patients With Advanced Digestive System Tumors

A Prospective, Open-label, Exploratory Basket Trial to Evaluate the Efficacy and Safety of Sintilimab Combined With Pyrotinib ± Chemotherapy in Patients With Advanced Digestive System Tumors (CCGLC-018)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Tongji Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, open-label, exploratory, phase II basket clinical trial designed to evaluate the efficacy and safety of sintilimab in combination with pyrotinib with or without chemotherapy in patients with advanced HER2-positive digestive system malignancies. Eligible patients include those with locally advanced unresectable or metastatic gastric, colorectal, hepatocellular, biliary tract, or pancreatic cancers. Patients will receive sintilimab and pyrotinib, with chemotherapy regimens selected at the investigator's discretion based on tumor type and clinical condition. The primary endpoint is objective response rate (ORR), with secondary endpoints including progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.

Detailed description

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has significantly advanced the treatment landscape for various solid tumors, but many patients still fail to respond or develop resistance. Combining ICIs with targeted agents may overcome these limitations. Pyrotinib is a pan-ErbB irreversible tyrosine kinase inhibitor (TKI) with potent activity against HER2, which is overexpressed in multiple digestive tract cancers including gastric, colorectal, biliary tract, and pancreatic cancers. This basket trial investigates the efficacy and safety of sintilimab (a PD-1 inhibitor) combined with pyrotinib, with or without chemotherapy, in HER2-positive digestive system tumors. Patients must meet HER2 positivity criteria via IHC, FISH/CISH, or NGS. The study uses a Bayesian adaptive design to independently evaluate efficacy across cancer subtypes. Patients will receive sintilimab (200 mg IV every 3 weeks) and pyrotinib (400 mg orally daily). Chemotherapy is optional and tailored by tumor type, including regimens such as FOLFOX, GC, XELOX, or AG, among others. Primary endpoint: ORR per RECIST 1.1. Secondary endpoints: PFS, DCR, OS, and treatment-related adverse events (TRAEs). The total planned enrollment is approximately 80 patients, with flexible sample size adjustments based on interim Bayesian analysis within each tumor cohort. Exploratory objectives include biomarker analysis (e.g., PD-L1, TMB, HER2 amplification/mutation) and tumor microenvironment changes.

Conditions

• Advanced Digestive System Tumor

Interventions

Type	Name	Description
DRUG	Sintilimab	Dosage Form: Intravenous (IV) infusion Dosage: 200 mg Frequency: Every 3 weeks (Q3W) Duration: Until disease progression, unacceptable toxicity, or up to 2 years
DRUG	Pyrotinib	Dosage Form: Oral tablet Dosage: 400 mg once daily (QD) Frequency: Continuous daily dosing Duration: Until disease progression or intolerable toxicity
DRUG	Optional Chemotherapy	1. FOLFOX: Oxaliplatin 85 mg/m² IV Day 1, leucovorin 400 mg/m² IV Day 1, 5-FU 400 mg/m² IV bolus + 2400 mg/m² continuous infusion over 46h (Days 2-3) 2. GEMOX: Gemcitabine 1000 mg/m² and oxaliplatin 100 mg/m² IV Day 1 3. GC: Gemcitabine 1000 mg/m² and cisplatin 25 mg/m² IV on Days 1 and 8 4. XELOX (CapeOX) Oxaliplatin 130 mg/m² IV Day 1, capecitabine 1000 mg/m² PO BID Days 1-14 5. SOX: Oxaliplatin 130 mg/m² IV Day 1, S-1 PO BID Days 1-14 (dose based on BSA: \<1.25 m² = 40 mg, 1.25-\<1.5 m² = 50 mg, ≥1.5 m² = 60 mg) 6. TS: Paclitaxel 80 mg/m² IV Days 1 and 8, S-1 as above 7. mFOLFOX6: Same as FOLFOX; used primarily in colorectal cancer 8. FOLFIRINOX: Leucovorin 400 mg/m², 5-FU (bolus + continuous), irinotecan 180 mg/m², oxaliplatin 85 mg/m² IV Day 1 9. AG: Nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² IV on Days 1 and 8

Timeline

• Start date: 2025-08-15
• Primary completion: 2030-12-31
• Completion: 2031-04-01
• First posted: 2025-07-08
• Last updated: 2025-07-08

Locations

1 site across 1 country: China