A prospective, single-arm clinical study of icaritin in combination with gemcitabine and nab-pacitaxel in patients with advanced pancreatic ductal adenocarcinoma not received prior systemic therapy.

e16362 Background: Pancreatic cancer is recognized as one of the most lethal malignant neoplasm, with approximately 80% of patients presenting with advanced-stage disease at the time of diagnosis, rendering them ineligible for surgical intervention. Among these patients with initially unresectable, only 20% may subsequently qualify for surgical resection following conversion therapy. The gemcitabine and nab-palitaxel(AG) is represents one of the vital therapeutic modalities for treating the advanced pancreatic cancer. Icaritin, a phytochemical molecular, has demonstrated immunomodulatory and anti-inflammatory effects through the modulation of critical signaling pathways. In this study, we investigated the efficacy and safety of Icaritin administered in conjunction with AG in patients newly diagnosed with advanced pancreatic ductal adenocarcinoma (PDAC). Methods: This is a single-arm, single-center prospective study, which enroll a total of 20 newly diagnosed advanced PDAC patients. All the patients are suggested to receive 6-cycle of the combo therapy consisting of Icaritin with AG. The primary endpoint is the progression-free survival(PFS) and the secondary endpoints include objective response rate(ORR), overall survival(OS), 6-month survival rate, 12-month survival rate, disease control rate(DCR), duration of response(DOR), and treatment-related adverse events(TRAEs). All the endpoints will be assessed by the investigator. Results: During November 2023 and October 2024, we recruited 23 patients, 3 of whom were excluded for refusal of treatment with Icaritin. Among the 20 patients enrolled, metastatic conditions included liver metastases, peritoneal metastases, tumor-induced vascular invasion of arterial and venous resulting to ineligibility for surgical resection. The median age was 63.55 years(range 39-76), of those 3 were female. As the data cutoff date on December 15, 2024, the primary endpoint was not met, 10 and 8 patients achieved PR and SD, respectively. Demonstrated an ORR and DCR were 50% and 90%, respectively. 6-month survival rate was 90%. In addition, 7 patients who were initially uresectable became resectable during the treatment and the success of conversion therapy is 35%. For the safety information, the incidence of TRAEs Grade≥3 was 40%(8/20), mainly chemotherapy associated, with neutropenia (55%), and anemia (25%), thrombocytopenia (20%), hypokalemia (15%), and rash (15%) as the most common TRAEs. No TRAE leading to death occurred. More data would be further analyzed and reported. Conclusions: Although trials with larger sample size are needed for further validation, this experimental phase II study indicates Icaritin as a promising role in combination with chemotherapy for the treatment of advanced PDAC. Clinical trial information: ChiCTR2300077907 .