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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-08-15

Study Completion Date

2031-04-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Escalating Doses of PM01183 in Combination With Gemcitabine in Patients With Specific Unresectable Solid Tumors

NCT01970553

Specific Advanced Solid Tumors

COMPLETED PHASE1

Pazopanib in Advanced and Cisplatin-resistant Germ Cell Tumors

NCT01743482

Germ Cell Tumors Measurable Disease

COMPLETED PHASE2

Gemcitabine and Pazopanib in Chemotherapy Naïve Patients With Advanced/Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Chemotherapy

NCT01622660

Bladder Cancer

TERMINATED PHASE2

S0101 Gemcitabine and Irinotecan in Treating Patients With Metastatic or Recurrent Cancer of the Esophagus

NCT00012363

Esophageal Cancer Gastric Cancer

COMPLETED PHASE2

Gemox Combined With Anlotinib and Sintilimab in Advanced cHCC-ICC

NCT06033118

Combined Hepatocellular Cholangiocarcinoma

NOT_YET_RECRUITING PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Advanced Digestive System Tumor

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

HER2-Positive Gastric Cancer

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.

Group Type EXPERIMENTAL

Sintilimab

Intervention Type 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

Pyrotinib

Intervention Type DRUG

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

Optional Chemotherapy

Intervention Type 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 Colorectal Cancer

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.

Group Type EXPERIMENTAL

Sintilimab

Intervention Type 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

Pyrotinib

Intervention Type DRUG

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

Optional Chemotherapy

Intervention Type 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 Hepatocellular Carcinoma

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.

Group Type EXPERIMENTAL

Sintilimab

Intervention Type 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

Pyrotinib

Intervention Type DRUG

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

Optional Chemotherapy

Intervention Type 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

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.

Group Type EXPERIMENTAL

Sintilimab

Intervention Type 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

Pyrotinib

Intervention Type DRUG

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

Optional Chemotherapy

Intervention Type 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 Pancreatic Cancer

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).

Group Type EXPERIMENTAL

Sintilimab

Intervention Type 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

Pyrotinib

Intervention Type DRUG

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

Optional Chemotherapy

Intervention Type 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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type DRUG

Pyrotinib

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

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Anti-PD-1 Monoclonal Antibody Pan-HER Tyrosine Kinase Inhibitor

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Active tuberculosis requiring treatment or treated within past year
* Major surgery within 4 weeks or unhealed surgical wounds
* Severe dysfunction of major organs (heart, lungs, liver, kidneys, CNS)
* Any other condition that may increase risk or interfere with study results as judged by investigator

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No