A Phase I Study Of Nanoliposomal Irinotecan And 5-Fluorouracil/Folinic Acid In Combination With Interleukin-1-Alpha Antagonist For Advanced Pancreatic Cancer Patients With Cachexia (Onfx)

TPS780 Background: Patients with pancreatic cancer have the highest rate of weight loss among all advanced cancers. Of which, the majority develop cachexia, characterized by progressive and involuntary loss of weight and skeletal muscle mass. In preclinical studies, interleukin-1-alpha (IL-1α) antagonism has been found to neutralize tumor angiogenesis and onco-inflammation. Early phase single-agent studies in cancer cachexia have demonstrated increased lean body mass and decreased fatigue, pain, and appetite loss. The present study aims to establish the safety of an IL-1α antagonist (Bermekimab) in combination with nanoliposomal irinotecan (Nal-Iri) and 5-fluorouracil (5FU)/folinic acid (FA) in patients with advanced pancreatic adenocarcinoma and cachexia who have failed gemcitabine-based chemotherapy. Methods: This is a single arm, single center, phase I study. The primary objective is to assess the maximum tolerated dose (MTD) of Bermekimab in combination with Nal-Iri and 5FU/FA. MTD is defined as the dose such that the probability of dose-limiting toxicities at MTD is θ = 0.33. The first cohort of up to 3 patients will receive 7.5 mg/kg Bermekimab, 50 mg/m2 nanoliposomal irinotecan, 2000 mg/m2 5FU, and 400 mg/m2 FA and the subsequent doses will be determined by the escalation with overdose control (EWOC) algorithm. Treatment is administered on days 1 and 15 of each 28-day cycle. Key inclusion criteria include: advanced or locally advanced pancreatic adenocarcinoma that has progressed through or intolerant of gemcitabine-based chemotherapy, cachexia defined as > 5% unexplained weight loss 6 months prior to screening or as documented by physician, ECOG PS 0-2 or KPS ≥ 60%, and normal organ and marrow function. Secondary objectives are to assess weight, lean body mass, inflammatory cytokines, overall survival, progression free survival, patient quality of life, and functional status. Since January 2019, 23 patients have been screened and 21 enrolled. Clinical trial information: NCT03207724.