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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
56
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.
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.
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.
Shanghai Zhongshan Hospital
Shanghai, China
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.
Time frame: From the first dose through 12 months
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).
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: From signing informed consent through 30 days after the last study treatment or initiation of new anticancer therapy, whichever occurs first
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