Regorafenib with toripalimab and albumin‑bound paclitaxel for third‑line advanced pancreatic cancer

A Phase Ib/II Clinical Study of Regorafenib Combined With Toripalimab and Albumin-bound Paclitaxel for the Third-line Treatment of Advanced Pancreatic Cancer

This trial will test whether adding regorafenib to toripalimab and albumin‑bound paclitaxel helps people with unresectable or metastatic pancreatic cancer who have already received two prior lines of therapy.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center (Academic / other)
• Drugs / interventions: Toripalimab, Terriptylimab
• Locations: 1 site (Shenzhen, Guangdong)
• Trial ID: NCT07040228 on ClinicalTrials.gov

What this trial studies

This is a Phase Ib/II interventional trial that first uses a Phase Ib dose‑escalation design to find the maximum tolerated dose and recommended Phase II dose of oral regorafenib given with intravenous toripalimab and albumin‑bound paclitaxel. Regorafenib is given orally at planned dose levels of 40, 80, and 120 mg per day on days 1–14 of a 21‑day cycle, toripalimab 240 mg IV on day 1 of each 21‑day cycle, and albumin‑bound paclitaxel 125 mg/m2 IV on days 1 and 8 of each cycle. In Phase II patients receive the recommended regorafenib dose together with the same toripalimab and paclitaxel schedule and are treated until disease progression or unacceptable toxicity. The trial is sponsored by the Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center, and conducted at that single site in Shenzhen, Guangdong.

Who should consider this trial

Good fit: Adults aged 18–80 with histologically confirmed unresectable or metastatic pancreatic cancer who have progressed after standard first‑ and second‑line treatments, have at least one measurable lesion, ECOG 0–2, expected survival ≥2 months, and adequate blood, liver, and kidney function are eligible.

Not a fit: Patients with poor performance status (ECOG >2), expected survival under two months, significant organ dysfunction, or those not able to travel to the Shenzhen site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this combination could provide a new treatment option that prolongs disease control or survival for patients whose pancreatic cancer progressed after two prior regimens.

How similar studies have performed: Combining anti‑angiogenic agents, immunotherapy, and chemotherapy has shown limited but sometimes encouraging signals in early‑phase trials for various solid tumors, yet triple therapy in late‑line pancreatic cancer remains largely experimental with no established proof of major benefit.

Eligibility criteria

Inclusion Criteria:

1. The patient fully understands this study, voluntarily participates and signs an informed consent form (ICF);
2. Age ≥ 18 years old and ≤ 80 years old;
3. Patients with unresectable/metastatic pancreatic cancer confirmed by histopathology;
4. Imaging confirmation of tumor progression after previous first-line and second-line standard treatment;
5. According to RECIST 1.1 criteria, patients must have at least one measurable target lesion;
6. Eastern Cancer Collaboration Group (ECOG) Physical Fitness Status Score: 0-2 points;
7. Expected survival time ≥ 2 months;
8. Absolute neutrophil count (ANC) ≥ 1.5 × 10 \^ 9/L, platelets ≥ 100 × 10 \^ 9/L, and hemoglobin ≥ 90 g/L (No blood transfusion or blood products within 14 days prior to laboratory examination.

   Not treated with granulocyte colony-stimulating factor or other hematopoietic stimulating factors);
9. Liver and kidney function: serum creatinine ≤ 1.5 times the upper limit of normal value; AST and ALT ≤ 2.5 times the upper limit of normal values (≤ 5 times the upper limit of normal values for patients with liver metastases); Total bilirubin ≤ 1.5 times the upper limit of normal value (≤ 3 times the upper limit of normal value for patients with liver metastasis);
10. Women of childbearing age must undergo a pregnancy test (serum) within 7 days before enrollment, and the result must be negative, And willing to use appropriate contraception methods during the trial period and 6 months after the last administration of the trial drug.

Exclusion Criteria:

1. Have hypersensitivity reactions to any research drug or its components;
2. Concurrent serious uncontrolled infections or other serious uncontrolled accompanying diseases, moderate or severe kidney injury; (such as progressive infection, uncontrollable hypertension, diabetes, etc.);
3. Heart function and disease meet one of the following conditions:

   1. Long QTc syndrome or QTc interval\>480 ms;
   2. Complete left bundle branch block, grade II or III atrioventricular block;
   3. Severe and uncontrolled arrhythmias requiring medication treatment;
   4. New York College of Cardiology classification ≥ III;
   5. Heart ejection fraction (LVEF) below 50%;
   6. History of myocardial infarction, unstable angina, and severe unstable ventricular arrhythmia within 6 months prior to recruitment or any other arrhythmia requiring treatment, history of clinically severe pericardial disease, or there may be electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
4. Active infection of hepatitis B and C (hepatitis B virus surface antigen is positive and hepatitis B virus DNA exceeds 1x103 copies/mL; Hepatitis C virus RNA exceeding 1x103 copies/mL).Asymptomatic chronic carriers of hepatitis B or hepatitis C excluded;
5. Human immunodeficiency virus (HIV) infection (HIV antibody positive);
6. Imaging confirms intestinal obstruction;
7. Previously or currently suffering from other malignant tumors simultaneously (Except for non melanoma basal cell carcinoma and breast/cervical carcinoma in situ that have been effectively controlled and other malignant tumors that have been effectively controlled without treatment in the past five years);
8. Pregnant and lactating women, as well as reproductive age patients who are unwilling to take contraceptive measures;
9. Patients who require treatment for merging with other malignant tumors;
10. History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as at least 2.5mL of bright red blood) within one month prior to the first administration;
11. Within 6 months prior to the first administration, there are arterial embolism, severe bleeding (excluding bleeding caused by surgery), and a tendency for severe bleeding;
12. Merge symptomatic brain metastases, meningeal metastases, spinal cord tumor invasion, and spinal cord compression syndrome;
13. Have used other clinical trial drugs within one month before the first administration;
14. The researchers have determined that patients who are not suitable to participate in this study.

Where this trial is running

Shenzhen, Guangdong

• Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center — Shenzhen, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Hang Junjie, doctorate

Conditions Pancreatic Cancer Metastatic; Efficacy; Safety; Advanced pancreatic cancer; Regorafenib; Toripalimab