Data from Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma

• DOI: 10.1158/1078-0432.c.6529928.v1
• Publication Date: 2023-04-01T06:18:15Z
• Authors: Christine Alewine; Mehwish Ahmad; Cody J. Peer; Zishuo I. Hu; Min-Jung Lee; Akira Yuno; Jessica D. Kindrick; Anish Thomas; Seth M. Steinberg; Jane B. Trepel; William D. Figg; Raffit Hassan; Ira Pastan
• Keywords: Mesothelin; Pseudomonas exotoxin

<div>AbstractPurpose:<p>LMB-100 is a recombinant immunotoxin (iTox) consisting of mesothelin-binding Fab for targeting and modified <i>Pseudomonas</i> exotoxin A payload. Preclinical studies showed that combining taxanes with iTox results in synergistic antitumor activity. The objectives this phase I/II study were to determine the MTD LMB-100 when administered nanoalbumin bound (nab)-paclitaxel patients previously treated advanced pancreatic adenocarcinoma assess objective response rate.</p>Patients Methods:<p>Patients (<i>n</i> = 20) received fixed-dose nab-paclitaxel (125 mg/m<sup>2</sup> on days 1 8) (65 or 100 μg/kg 1, 3, 5) 21-day cycles 1–3 cycles.</p>Results:<p>Fourteen dose escalation an additional six II expansion. 65 was established combination. Dose-limiting toxicity resulting from capillary leak syndrome (CLS) seen two five at one evaluable I receiving MTD. Severity CLS associated increases apoptotic circulating endothelial cells. exposure unaffected by anti-LMB-100 antibody formation 13 during cycle 2. Seven 17 experienced >50% decrease CA 19-9, including three previous nab-paclitaxel. One patient developed partial response. Patients biomarker responses had higher tumor mesothelin expression.</p>Conclusions:<p>Although clinical activity observed, combination not well tolerated alternative drug combinations will be pursued.</p></div>