Abstract CT086: Phase II study of Minnelide for patients with adenosquamous carcinoma of the pancreas (ASCP)

Abstract ASCP is a rare and highly aggressive variant of pancreatic ductal adenocarcinoma (PDAC) with especially poor prognosis because it is frequently refractory to standard chemotherapy. Previous work has demonstrated that upregulation of the Myc oncogene is an important driver of ASCP. Minnelide is an oral superenhancer inhibitor drug that downregulates Myc expression in ASCP and PDAC and is safe to administer to patients. In this Phase II, single institution, open label, single arm study, patients with previously treated, RECIST-measurable, advanced ASCP were treated with oral Minnelide (2mg daily (n=8), 2.5mg daily (n=4), for 21 days of a 28-day cycle) until progression or intolerable toxicity. The primary objective was disease control at 16 weeks, with an early stopping rule to halt enrollment if <3 of the first 12 participants reached this benchmark. Secondary objectives included safety, progression free survival (PFS), and overall survival (OS). Eligible participants received treatment (n = 12, 75% male, median age 69.5 years [range: 49-85]) at the NIH Clinical Center. Three participants had best response of stable disease with 1 participant (receiving 2.5mg dose) meeting the 16-week milestone for clinical benefit. One additional participant (2.5mg dose) remains on treatment with stable disease. The median PFS and OS among study participants who have completed treatment were 6.3 weeks (range: 2-24) and 16 weeks (range: 2-74+), respectively. Circulating tumor cells decreased in 6 of the 9 patients with evaluable serial samples. Eight severe adverse events attributed to Minnelide occurred in 7 participants including nausea, dehydration, anemia, upper GI hemorrhage, infection, dyspnea, and balance problem. Treatment-related adverse events experienced by at least 25% of participants were nausea, vomiting, diarrhea, anorexia, thrombocytopenia, anemia, neutropenia, fever/ chills, fatigue or malaise, dysphagia/ esophageal spasm, and fall. In summary, at interim analysis, Minnelide treatment at this lower dose did not meet the efficacy endpoint for study continuation in participants with this difficult to treat variant of pancreatic cancer. Further testing at 2.5mg or higher doses may be warranted. Citation Format: Christine Campo Alewine, Laura Yee, Muhammad S. Alam, Renee N. Donahue, Min-Jung Lee, Sunmin Lee, Nahoko Sato, Shraddha Rastogi, Roshan L. Shrestha, Derek Cridebring, Haiyong Han, Daniel D. Von Hoff, Nebojsa Skorupan. Phase II study of Minnelide for patients with adenosquamous carcinoma of the pancreas (ASCP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT086.