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

NCT07053150 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-S045
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Digestive System Tumor

Keywords

Pyrotinib; Sintilimab; HER2-Positive Advanced digestive system tumors; HER2-positive tumors; Immunotherapy; Targeted therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Proportion of patients achieving complete response (CR) or partial response (PR) as assessed by investigators according to RECIST v1.1. Responses must be confirmed by repeat imaging ≥4 weeks (±7 days) after the initial documentation.

  Up to 24 months.

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  Up to 36 months.

• Disease Control Rate (DCR)

  Up to 24 months.

• Overall Survival (OS)

  Up to 36 months.

• Treatment-Related Adverse Events (TRAEs)

  From first dose through 90 days after last dose.

Other Outcomes (2)

• Biomarker Analysis (PD-L1, TMB, HER2 Amplification)

  Baseline (pre-treatment) and at time of disease progression (if re-biopsied), assessed up to 36 months.

• Tumor Microenvironment Changes (CD8+ T Cells, Tregs)

  Baseline (pre-treatment) and at time of disease progression (if re-biopsied), assessed up to 36 months.

Study Arms (5)

HER2-Positive Gastric Cancer

EXPERIMENTAL

Patients with HER2-positive advanced or metastatic gastric cancer will receive sintilimab (200 mg IV, Q3W) and pyrotinib (400 mg PO, QD), with or without chemotherapy. The investigator may choose from XELOX, SOX, or TS regimens based on clinical evaluation.

Drug: Sintilimab; Drug: Pyrotinib; Drug: Optional Chemotherapy

HER2-Positive Colorectal Cancer

EXPERIMENTAL

Patients with HER2-positive advanced or metastatic colorectal cancer will receive sintilimab (200 mg IV, Q3W) and pyrotinib (400 mg PO, QD), with or without chemotherapy. The recommended regimens include mFOLFOX6 or XELOX, at the investigator's discretion.

Drug: Sintilimab; Drug: Pyrotinib; Drug: Optional Chemotherapy

HER2-Positive Hepatocellular Carcinoma

EXPERIMENTAL

Patients with HER2-positive advanced or unresectable hepatocellular carcinoma will receive sintilimab (200 mg IV, Q3W) and pyrotinib (400 mg PO, QD), with or without chemotherapy. Chemotherapy may include FOLFOX or interventional locoregional therapies, as appropriate.

Drug: Sintilimab; Drug: Pyrotinib; Drug: Optional Chemotherapy

HER2-Positive Biliary Tract Cancer

EXPERIMENTAL

Patients with HER2-positive advanced or metastatic biliary tract cancer (including intrahepatic and extrahepatic cholangiocarcinoma, gallbladder cancer) will receive sintilimab (200 mg IV, Q3W) and pyrotinib (400 mg PO, QD), with or without chemotherapy. Suggested regimens include GC (gemcitabine + cisplatin) or GEMOX.

Drug: Sintilimab; Drug: Pyrotinib; Drug: Optional Chemotherapy

HER2-Positive Pancreatic Cancer

EXPERIMENTAL

Patients with HER2-positive advanced or metastatic pancreatic cancer will receive sintilimab (200 mg IV, Q3W) and pyrotinib (400 mg PO, QD), with or without chemotherapy. Optional chemotherapy regimens include FOLFIRINOX or AG (nab-paclitaxel + gemcitabine).

Drug: Sintilimab; Drug: Pyrotinib; Drug: Optional Chemotherapy

Interventions

Sintilimab DRUG

Dosage Form: Intravenous (IV) infusion Dosage: 200 mg Frequency: Every 3 weeks (Q3W) Duration: Until disease progression, unacceptable toxicity, or up to 2 years

Also known as: Anti-PD-1 Monoclonal Antibody

HER2-Positive Biliary Tract Cancer; HER2-Positive Colorectal Cancer; HER2-Positive Gastric Cancer; HER2-Positive Hepatocellular Carcinoma; HER2-Positive Pancreatic Cancer

Pyrotinib DRUG

Dosage Form: Oral tablet Dosage: 400 mg once daily (QD) Frequency: Continuous daily dosing Duration: Until disease progression or intolerable toxicity

Also known as: Pan-HER Tyrosine Kinase Inhibitor

HER2-Positive Biliary Tract Cancer; HER2-Positive Colorectal Cancer; HER2-Positive Gastric Cancer; HER2-Positive Hepatocellular Carcinoma; HER2-Positive Pancreatic Cancer

Optional Chemotherapy DRUG

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

HER2-Positive Biliary Tract Cancer; HER2-Positive Colorectal Cancer; HER2-Positive Gastric Cancer; HER2-Positive Hepatocellular Carcinoma; HER2-Positive Pancreatic Cancer

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years
• Patients with unresectable locally advanced T3-4 stage or M1 stage metastatic digestive system tumors confirmed by histology or cytology, including gastric cancer, colorectal cancer, hepatocellular carcinoma, biliary tract cancer and pancreatic cancer
• Patients who have not received systematic treatment in the past or whose disease has progressed or is intolerant after standard first-line treatment, and whose disease has progressed for more than 6 months after neoadjuvant therapy/whose last adjuvant therapy failed/who have completed (new) adjuvant therapy for less than 6 months from disease recurrence can be enrolled
• Histologically or cytologically confirmed HER2-positive (IHC 3+ or IHC 2+/FISH-amplified/NGS-confirmed) locally advanced or metastatic digestive system tumors (including gastric, colorectal, hepatocellular, biliary tract cancers)
• ECOG performance status 0-2
• At least one measurable lesion per RECIST 1.1 criteria
• Adequate organ function:
• Hematologic: ANC ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥9 g/dL
• Hepatic: Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN (≤5×ULN for liver metastases/HCC); albumin ≥28 g/L
• Renal: Serum creatinine ≤1.5×ULN or CrCl ≥50 mL/min; urine protein \<2+ (if ≥2+, 24-hour urine protein \<1 g)
• Coagulation: INR ≤2.3 or PT prolongation ≤6 seconds
• Life expectancy ≥12 weeks
• Fertile patients must use effective contraception during treatment and for 6 months after last dose
• Willing and able to provide written informed consent

You may not qualify if:

• Previous treatment with any HER2-targeted therapy (e.g., trastuzumab)
• History of hematologic malignancies
• Pregnancy, lactation, or plans to become pregnant during study
• Last anticancer therapy ≤28 days prior to enrollment or unresolved toxicities from prior therapy
• Contraindications to immunotherapy including:
• History of organ transplantation
• Severe autoimmune diseases
• Grade ≥4 immune-related adverse events from prior immunotherapy
• Uncontrolled active infections
• Use of systemic immunosuppressants (\>10 mg/day prednisone equivalent) within 14 days
• Known hypersensitivity to PD-1 inhibitors, pyrotinib, or monoclonal antibodies
• Participation in other clinical trials within 3 months
• Symptomatic ascites, pleural or pericardial effusion requiring drainage
• Life-threatening bleeding events within 3 months or arterial/venous thrombosis within 6 months (except stable catheter-related thrombosis)
• History of pulmonary fibrosis, interstitial lung disease, or drug-related pneumonitis

Sponsors & Collaborators

• Tongji Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Interventions

sintilimab; spartalizumab; pyrotinib

Study Officials

• Ze-yang Ding, M.D.

  Tongji Hospital

  STUDY CHAIR

Central Study Contacts

Ze-yang Ding, M.D.

CONTACT

+86 13407156200; zyding@tjh.tjmu.edu.cn

Han Gao

CONTACT

+86 17730117747; gh1023606887@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 8, 2025
• Study Start: August 15, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): April 1, 2031
• Last Updated: July 8, 2025

Record last verified: 2025-07

Locations

CN (1)