Borderline Resectable Pancreatic CancerPhase 2ZSPAC-22NCT07833241
Surufatinib in Combination With Iparomlimab and Tuvonralimab Injection and AG Chemotherapy for Neoadjuvant Therapy of HRPC or BRPC
A Phase 2 study testing Surufatinib Plus Iparomlimab and Tuvonralimab and AG Chemotherapy, Gemcitabine plus Capecitabine and Modified FOLFIRINOX in people with Borderline Resectable Pancreatic Cancer and High-Risk Resectable Pancreatic Cancer, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
This is a prospective, single-center, single-arm phase 2 study evaluating the efficacy and safety of neoadjuvant surufatinib plus iparomlimab and tuvonralimab injection and nab-paclitaxel/gemcitabine chemotherapy in patients with high-risk resectable or borderline resectable pancreatic cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Borderline Resectable Pancreatic Cancer, High-Risk Resectable Pancreatic Cancer
- What is being tested?
- Surufatinib Plus Iparomlimab and Tuvonralimab and AG Chemotherapy, Gemcitabine plus Capecitabine and Modified FOLFIRINOX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2026to 1 Sep 2029
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have fully understood this study and voluntarily signed the informed consent form.
- Aged between 18 and 75 years inclusive, of any gender.
- Patients with high-risk resectable or borderline resectable pancreatic adenocarcinoma confirmed by histopathology or cytology. (The definition of borderline resectable pancreatic pancreatic cancer refers to the NCCN Guidelines 2026 (Version 1). High-risk resectable disease is defined as meeting all three of the following criteria:
- ① The tumor does not abut the portal vein-superior mesenteric vein (PV-SMV), or abuts the PV-SMV for <180° with intact venous contour.
- ② The tumor does not abut arteries (celiac trunk, superior mesenteric artery, or common hepatic artery).
- ③ CA19-9 ≥ 500 U/mL or maximum diameter of primary tumor > 3.0 cm.
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- Have at least one measurable lesion per RECIST 1.1.
- No pathogenic BRCA1/2 or PALB2 mutations, or unknown BRCA1/2 and PALB2 mutation status.
- No prior systemic anti-tumor therapy or locoregional radiotherapy.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Expected survival ≥ 24 weeks.
- Absence of contraindications to surgery.
- Laboratory hematology parameters (without blood transfusion within the preceding 14 days):
- ① Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelets ≥ 100 × 10⁹/L; hemoglobin ≥ 9 g/dL.
- ② Liver function: AST and ALT ≤ 2.5 × upper limit of normal (ULN); total bilirubin ≤ 1.5 × ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN.
- ③ Renal function: serum creatinine ≤ 1.5 × ULN; creatinine clearance (CCr) ≥ 60 mL/min.
- ④ Coagulation parameters: international normalized ratio (INR) ≤ 1.5 × ULN; prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
- Male and female patients of reproductive potential agree to use effective contraceptive methods throughout the study period and for 6 months after the last study drug administration, such as dual-barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered of reproductive potential unless they have natural menopause, induced menopause, or sterilization procedures (e.g., hysterectomy, bilateral adnexectomy, ovarian radiation, etc.).
Who cannot join
- Patients with distant metastasis.
- Patients who have received blood transfusion, blood products or hematopoietic growth factors (such as albumin and granulocyte colony-stimulating factor [G-CSF]) within 14 days prior to enrollment.
- Patients who have undergone any surgery or invasive treatment/procedure within 4 weeks prior to enrollment (except venous catheterization, puncture and drainage, etc.).
- Known hypersensitivity to any study drug.
- Uncontrolled hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg.
- Patients with any disease or condition affecting drug absorption, or patients unable to receive oral surufatinib.
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- Patients with active gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors, or other conditions judged by the investigator to carry risks of gastrointestinal bleeding or perforation.
- Uncontrolled malignant ascites (defined as ascites that cannot be controlled by diuretics or paracentesis as assessed by the investigator).
- Patients with evidence or history of obvious bleeding tendency within 3 months prior to enrollment (bleeding >30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (fresh blood >5 mL within 4 weeks), or thromboembolic events within 10 months (including stroke and/or transient ischemic attack [TIA]).
- Clinically significant electrolyte abnormalities as judged by the investigator.
- Significant clinically relevant cardiovascular diseases, including but not limited to: acute myocardial infarction, severe/unstable angina or coronary artery bypass grafting within 6 months prior to enrollment; New York Heart Association (NYHA) class >2 congestive heart failure; ventricular arrhythmias requiring pharmacological treatment; left ventricular ejection fraction (LVEF) <50%.
- History of other malignancies within the past 5 years, except for radically resected basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
- Active or uncontrolled severe infections:
- ①Known human immunodeficiency virus (HIV) infection;
- ②Known history of clinically significant liver disease, including viral hepatitis. ③Known hepatitis B virus (HBV) carriers must be excluded if there is active HBV infection, i.e., positive HBV DNA (>1×10⁴ copies/mL or >2000 IU/mL); Known hepatitis C virus (HCV) infection with positive HCV RNA (>1×10³ copies/mL), or other hepatitis, liver cirrhosis.
- Pregnant females (positive pregnancy test prior to study drug administration) or lactating females.
- The investigator judges that the subject has any clinical or laboratory abnormality or other conditions rendering the subject unsuitable for participation in this clinical study.
- Urinalysis showing urine protein ≥2+, with 24-hour urinary protein quantification >1.0 g.
- Patients with active autoimmune or inflammatory diseases requiring systemic therapy within the previous 2 years (i.e., disease-modifying agents, glucocorticoids or immunosuppressive agents); or diseases treated with long-term systemic hormones or any other immunosuppressive drugs (excluding inhaled corticosteroids).
- Patients with hypothyroidism/adrenal or pituitary insufficiency who only require stable hormone replacement therapy, as well as patients with type 1 diabetes mellitus with stable disease managed solely by insulin replacement, are eligible for enrollment.
- History of (non-infectious) pneumonia requiring steroid treatment; past or current history of interstitial lung disease, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, pulmonary fibrosis or other lung diseases resulting in severely impaired pulmonary function; or active pulmonary infection at present.
- Receipt of any live or attenuated live vaccine within 4 weeks before the first study drug administration, or planned administration of such vaccines during the study period.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai Zhongshan Hospital
Shanghai, 200000
Liang Liu, MD PhD, 021-64041990, liu.liang@zs-hospital.sh.cn
Xu Han, MD PhD, 021-64041990, han.xu1@zs-hospital.sh.cn
About this study
Official title: Neoadjuvant Surufatinib in Combination With Iparomlimab and Tuvonralimab Injection and AG Chemotherapy for High-risk Resectable or Borderline Resectable Pancreatic Cancer: a Single-arm, Single-center, Exploratory Clinical Study
This is a prospective, single-center, single-arm phase 2 study evaluating the efficacy and safety of neoadjuvant surufatinib plus iparomlimab and tuvonralimab injection and nab-paclitaxel/gemcitabine chemotherapy in patients with high-risk resectable or borderline resectable pancreatic cancer. Approximately 56 participants will be enrolled, including about 19 patients with high-risk resectable disease and 37 patients with borderline resectable disease. Participants will receive up to four 21-day cycles of neoadjuvant treatment. Participants considered eligible for surgery will undergo surgical resection approximately 4 weeks after neoadjuvant treatment. After surgery, adjuvant chemotherapy with either gemcitabine plus capecitabine or modified FOLFIRINOX will be selected by the investigators after multidisciplinary team review. The primary outcome is the 12-month event-free survival rate.
- Being tested
- Surufatinib Plus Iparomlimab and Tuvonralimab and AG Chemotherapy, Gemcitabine plus Capecitabine, Modified FOLFIRINOX
- Keywords
- Surufatinib, Iparomlimab and Tuvonralimab, Neoadjuvant, pancreatic cancer
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surufatinib Plus Iparomlimab and Tuvonralimab and AG ChemotherapyDrug
Surufatinib 200 mg orally once daily; iparomlimab and tuvonralimab injection 5 mg/kg intravenously every 21 days; nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, for up to four cycles.
Gemcitabine plus CapecitabineDrug
After surgery, eligible participants may receive gemcitabine 1000 mg/m² intravenously on Days 1 and 8 plus capecitabine 1650-2000 mg/m²/day orally on Days 1-14 of each 21-day cycle.
Modified FOLFIRINOXDrug
After surgery, eligible participants may receive oxaliplatin 85 mg/m², irinotecan 150 mg/m², leucovorin 400 mg/m², and fluorouracil 2400 mg/m² every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | All participants will receive up to four cycles of neoadjuvant surufatinib plus iparomlimab and tuvonralimab injection and AG chemotherapy. Eligible participants will undergo surgery approximately 4 weeks after neoadjuvant treatment. After surgery, participants will receive either GemCap or modified FOLFIRINOX adjuvant chemotherapy, as selected by the investigators. Receives: Drug: Surufatinib Plus Iparomlimab and Tuvonralimab and AG Chemotherapy; Drug: Gemcitabine plus Capecitabine; Drug: Modified FOLFIRINOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-month Event Free Survival (EFS) rate
The starting point is the day of the first dose of neoadjuvant therapy, and observation continues until any of the following events occur (whichever comes first): 1. Disease progression (RECIST 1.1; re-evaluation is allowed if immune-related pseudoprogression is suspected); 2. Failure to complete the planned neoadjuvant therapy; 3. Inability to undergo surgery (including for non-disease reasons) or positive surgical margins; 4. Found to be unresectable during surgery; 5. Death for any reason.
Measured: From the first dose through 12 months
Secondary outcomes (9)
Pathological complete remission rate (pCR)
In patients who underwent surgery after receiving neoadjuvant therapy, no remaining living tumor cells were found in the original tumor site or any regional lymph nodes in the surgical specimens (that is, ypT0N0).
Measured: At postoperative pathological assessment, approximately 4 months after the first dose
Major pathological remission rate (MPR)
This study defines patients who had surgery after receiving neoadjuvant therapy as having a proportion of remaining viable tumor cells in the resected tumor bed of ≤50% of the tumor bed area.
Measured: At postoperative pathological assessment, approximately 4 months after the first dose
Objective Response Rate (ORR)
Refers to the proportion of patients whose tumors shrink by a certain amount and maintain that reduction for a certain period, including cases of CR and PR. Tumor objective response is assessed using the solid tumor response evaluation criteria (RECIST 1.1). Subjects must have measurable tumor lesions at baseline, and efficacy evaluation standards according to RECIST 1.1 are classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).
Measured: Every 6 weeks (±7 days) from the first dose until disease progression or completion of neoadjuvant study treatment, assessed up to approximately 12 weeks.
Disease Control Rate (DCR)
The percentage of cases with complete response, partial response, or stable disease lasting more than 4 weeks among patients whose efficacy can be evaluated.
Measured: Every 6 weeks (±7 days) from the first dose until disease progression or completion of neoadjuvant study treatment, assessed up to approximately 12 weeks.
Event Free Survival (EFS)
The starting point is the day of the first dose of neoadjuvant therapy, and observation continues until any of the following events occur (whichever comes first): 1. Disease progression (RECIST 1.1; re-evaluation is allowed if immune-related pseudoprogression is suspected); 2. Failure to complete the planned neoadjuvant therapy; 3. Inability to undergo surgery (including for non-disease reasons) or positive surgical margins; 4. Found to be unresectable during surgery; 5. Death for any reason.
Measured: From the date of the first dose of neoadjuvant therapy to the first documented EFS event, assessed up to 36 months.
Overall Survival
Overall survival is defined as the time from enrollment to death from any cause. Participants who are alive at the last follow-up will be censored on the date they were last known to be alive.
Measured: From the date of enrollment until death from any cause, assessed up to 36 months.
R0 resection rate
The R0 resection rate refers to the proportion of surgery patients whose removed tissue shows no remaining tumor cells at any of the margins (both lateral and vertical) during postoperative pathology checks. Specifically, this means the margins are negative (margin ≥1mm, with no tumor invasion).
Measured: At postoperative pathological assessment, approximately 4 months after the first dose
Conversion surgery success rate
Among patients who received neoadjuvant therapy and completed surgical evaluation, the proportion of patients who ultimately successfully converted to feasible radical surgery. Radical surgery refers to surgery where the tumor can be completely removed and meets the R0 resection criteria.
Measured: At the time of surgery following completion of neoadjuvant treatment, approximately 4 months after the first dose
Incidence and Severity of Adverse Events
Adverse events will be graded according to NCI CTCAE version 6.0. Treatment-related adverse events will be followed until resolution, stabilization, or initiation of new anticancer therapy.
Measured: From signing informed consent through 30 days after the last study treatment or initiation of new anticancer therapy, whichever occurs first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Sep 2028 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Borderline Resectable Pancreatic CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Liang Liu, Shanghai Zhongshan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07833241
- Sponsor's protocol ID
- ZSPAC-22
- Acronym
- ZSPAC-22
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2026
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No