Updated results of a single-arm phase II clinical trial of gemcitabine, cisplatin, and nab-paclitaxel as neoadjuvant therapy for pancreatic ductal adenocarcinoma.

Abstract

e16468 Background: Neoadjuvant chemo approach is favored in resectable/borderline resectable (R/BR) pancreatic ductal adenocarcinoma (PDAC) to increase the proportion of patients receiving systemic therapy. Current standard regimens, modified Folinic acid, Fluorouracil, Irinotecan, Oxaliplatin (mFOLFIRINOX) and gemcitabine nab-paclitaxel (GN), yield a 33% major pathologic response rate [SWOG S1505]. The regimen of capecitabine, cisplatin, nab-paclitaxel and gemcitabine (PAXG) improved median event free survival compared to mFOLFIRINOX but was equally toxic. The addition of cisplatin to GN(GCN) achieved a clinical response in 71% of patients with metastatic PDAC in a phase Ib/II trial. We evaluated the efficacy and safety of a biweekly neoadjuvant GCN regimen in R/BR PDAC patients. Methods: This ongoing single-arm phase II trial (NCT06423326) aims to evaluate biweekly neoadjuvant GCN in 36 patients with biopsy-proven R/BR PDAC (ECOG 0-1, no prior therapy, adequate organ function). GCN (G 800 mg/m², C 25 mg/m², N 100 mg/m²) is administered IV on days 1 and 15 of 28-day cycle for 4 cycles. CT scans were repeated every 2 weeks, and surgery occurred within 21-42 days after last chemo dose. The primary endpoint is clinical response including biochemical ( > 50% decrease in CA19-9), radiographic, pathologic responses or stable disease leading to surgical resection. Secondary endpoints include R0 resection rates, pathological response, chemotherapy completion, and recurrence free survival. Results: Between Aug 2024 and Dec 2025, 14 patients were enrolled and 12 were analyzed. The median age was 70.5 years; 50% males, 50% ECOG PS of 0 and 75% resectable disease. Median CA 19-9 was 192 (range 2–1542) before the first cycle and 67 (range 2–848) after the fourth cycle of GCN. Of 12 patients, 11 completed the 4 cycles and 4 (25%) required a dose reduction. 75% had biochemical response, all had stable radiographic disease (83%) or partial response (17%). 9 (75%) completed surgery, 89% of those had R0 resection and 33% node-negative. Any pathologic response was observed in 66% and 33% had a major pathologic response. Most resected patients completed adjuvant chemotherapy (8,89%) and 4/9 (45%) recurred. Grade 3 adverse events occurred in 75% (9/12), and included constipation (18%), neutropenia (18%), thromboembolic events (18%), anemia (9%), skin rash (9%), muscle pain (9%) and surgical wound infection (9%); no grade 3 neuropathy, grade 4 toxicities or treatment-related deaths occurred. Conclusions: Neoadjuvant biweekly gemcitabine, cisplatin and nab-paclitaxel is safe with favorable tolerability and manageable toxicity in patients with R/BR PDAC. The regimen demonstrates promising clinical response and high rates of surgical resection with the potential to outperform the current standard regimens, supporting the ongoing trial and further research. Clinical trial information: NCT06423326 .