Pancreatic Cancer
Conditions
Brief summary
This is a prospective, single-arm, single-center exploratory clinical study. The purpose of this study is to evaluate the efficacy and safety of a triplet regimen-becotatug vedotin combined with anti-PD-1 and S-1-in patients with EGFR-positive advanced pancreatic cancer who have failed at least one line of standard systemic therapy. Pancreatic cancer is one of the most lethal malignancies, and patients who progress after first-line treatment have very limited effective options. The study plans to enroll 27 participants aged 18 years or older with histopathologically confirmed pancreatic cancer, evidence of recurrence or metastasis (or disease not amenable to complete surgical resection), EGFR positivity confirmed by immunohistochemistry, an ECOG performance status of 0 to 3, and at least one measurable target lesion. All participants will receive becotatug vedotin 2.0 mg/kg intravenously on Day 1 every three weeks, anti-PD-1 200 mg intravenously on Day 1 every three weeks, and oral S-1 40 to 60 mg twice daily on Days 1 to 14 followed by a 7-day rest, repeated every three weeks. Treatment will continue until disease progression, unacceptable toxicity, completion of 12 months of treatment, or other protocol-defined discontinuation criteria. Tumor response will be assessed by CT or MRI every 9 weeks according to RECIST v1.1, and safety will be assessed according to NCI-CTCAE version 5.0. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. The study duration is approximately 3 years, with participant enrollment planned from OCT. 2026 to OCT. 2027. All participants will receive active treatment; no placebo is included. This study addresses a major unmet medical need, as current second-line and later treatment options for advanced pancreatic cancer provide only limited benefit.
Interventions
DRUGBecotatug Vedotin
Becotatug vedotin 2.0 mg/kg administered intravenously on Day 1 of each 21-day cycle.
Anti-PD-1 antibody 200 mg administered intravenously on Day 1 of each 21-day cycle.
DRUGS-1
S-1 40 to 60 mg per dose according to body surface area, administered orally twice daily on Days 1 to 14 of each 21-day cycle, followed by a 7-day rest.
Sponsors
Ningbo Medical Center Lihuili Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
： 1. Understands the study procedures and content and voluntarily signs written informed consent. 2. Age: 18 years or older. 3. Histopathologically confirmed pancreatic cancer. 4. The participant must have evidence of recurrence or metastasis, or have been assessed as not amenable to complete surgical resection, and must have received at least one prior line of standard systemic pharmacotherapy. 5. EGFR positivity (1+/2+/3+) confirmed by immunohistochemistry. 6. ECOG performance status of 0 to 3. 7. The patient must have at least one measurable target lesion according to RECIST v1.1. 8. Adequate organ and bone marrow function; screening laboratory tests must meet all of the following criteria: hemoglobin greater than 9 g/dL without transfusion or erythropoietin within the preceding 14 days; absolute neutrophil count of 1.5 x 10\^9/L or higher without the use of granulocyte colony-stimulating factor within the preceding 14 days; platelets of 80 x 10\^9/L or higher without transfusion within the preceding 14 days; total bilirubin of 1.5 x upper limit of normal or less (up to 3 x upper limit of normal permitted for Gilbert syndrome), ALT and AST of 2.5 x upper limit of normal or less (5 x upper limit of normal permitted in the presence of liver metastases); serum creatinine of 1.5 x upper limit of normal or less, or creatinine clearance of 50 mL/min or higher according to the Cockcroft-Gault formula; adequate coagulation function, defined as an international normalized ratio or prothrombin time of 1.5 x upper limit of normal or less; and normal thyroid function, defined as thyroid-stimulating hormone within the normal range, although participants with an out-of-range baseline thyroid-stimulating hormone may be enrolled if total T3 (or FT3) and FT4 are within the normal range. 9. Expected survival of more than 3 months. 10. For women of childbearing potential, a negative urine or serum pregnancy test within 3 days before the first administration of study drug (Day 1 of Cycle 1). Women who are not of childbearing potential are defined as postmenopausal for at least 1 year, or surgically sterilized, or having undergone hysterectomy. If there is any risk of conception, all participants must use a contraceptive measure with an annual failure rate of less than 1% throughout the treatment period and for 120 days after the last dose of study drug. 11. The participant is able and willing to comply with the visits, treatment plan, laboratory tests and other study-related procedures specified in the protocol.
Exclusion criteria
： 1. Diagnosis of another malignant disease within 5 years before the first dose (excluding radically treated basal cell carcinoma and squamous cell carcinoma of the skin, and/or radically resected carcinoma in situ). 2. Previous treatment with an antibody-drug conjugate containing MMAE as the cytotoxic payload; previous use of S-1. 3. Current participation in an interventional clinical study, or receipt of another investigational drug or treatment with an investigational device within 4 weeks before the first dose. 4. Systemic treatment within 2 weeks before the first dose with a Chinese patent medicine having an antitumor indication, or with an immunomodulatory agent (including thymosin, interferon and interleukin), except for local administration for the control of pleural effusion. 5. Active autoimmune disease requiring systemic treatment (for example disease-modifying agents, glucocorticoids or immunosuppressants) within 2 years before the first dose. Replacement therapy (for example thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency) is not considered systemic treatment. 6. Radiological evidence of tumor invasion or infiltration of a major blood vessel, or a bleeding tendency assessed by the investigator or the radiologist. 7. Major surgery (excluding surgery performed for the purpose of biopsy) within 4 weeks before the first dose of study drug, or planned major surgery during the study period. 8. Serious non-healing wound, ulcer or fracture. 9. Minor surgery (outpatient or inpatient procedure requiring local anesthesia, including placement of a central venous catheter) within 48 hours before the first dose of study drug. 10. Current or recent (within 10 days before the first dose of study drug) continuous use for 10 days of aspirin (more than 325 mg/day) or of another non-steroidal anti-inflammatory drug known to inhibit platelet function. 11. Current or recent (within 10 days before the first dose of study drug) treatment for 10 consecutive days with a full-dose oral or parenteral anticoagulant or thrombolytic agent. Note: prophylactic low-dose anticoagulation is permitted provided the international normalized ratio is 1.5 or less, in which case low-dose warfarin (1 mg/day or less), low-dose heparin (12,000 U/day or less) or low-dose aspirin (100 mg/day or less) may be used for prophylactic purposes. 12. Hereditary bleeding tendency or coagulation disorder, or a history of thrombosis. 13. Clinically uncontrollable pleural or peritoneal effusion (participants who do not require drainage, or in whom the effusion does not increase significantly after 3 days without drainage, may be enrolled). 14. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation. 15. Known hypersensitivity to becotatug vedotin, anti-PD-1, or any active ingredient or excipient of these study drugs. 16. Incomplete recovery from the toxicity and/or complications of any prior intervention before the start of treatment, i.e. toxicity worse than grade 1 or above baseline, excluding alopecia or fatigue. 17. Known history of human immunodeficiency virus infection, i.e. positive for HIV 1/2 antibody. 18. Untreated active hepatitis B, defined as HBsAg positive with detectable HBV-DNA copy number above the upper limit of normal of the local laboratory. 19. Administration of a live vaccine within 30 days before the first dose (Day 1 of Cycle 1). Note: administration of an injectable inactivated seasonal influenza vaccine within 30 days before the first dose is permitted; intranasal live attenuated influenza vaccine is not permitted. 20. Any medical history, disease evidence, treatment or abnormal laboratory value likely to interfere with the study results or to prevent full participation in the study, or any other condition judged by the investigator to carry an unacceptable risk, including severe or uncontrolled systemic disease such as unstable angina, congestive heart failure, chronic heart failure of New York Heart Association class 2 or higher; any arterial thrombosis, embolism or ischemia within 6 months before enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack; poorly controlled blood pressure (systolic blood pressure above 140 mmHg or diastolic blood pressure above 90 mmHg); active tuberculosis; active or uncontrolled infection requiring systemic treatment; clinically active diverticulitis, abdominal abscess or gastrointestinal obstruction; or a psychiatric disorder precluding cooperation with treatment. 21. Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Every 9 weeks (every three treatment cycles) from the start of treatment until disease progression, death, or end of study, up to approximately 36 months. | Proportion of patients who achieve a complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator. ORR = (number of patients with CR or PR) / total number of patients × 100%. CR and PR are determined based on the best overall tumor response confirmed twice during the study. |
Countries
China
Outcome results
None listed