LAUSR

Purpose: LMB-100 recombinant immunotoxin (iTox) consists of a mesothelin-binding Fab for targeting and a modified Pseudomonas exotoxin A payload. Preclinical studies showed that combining taxanes with iTox results in synergistic antitumor activity. The primary objectives of this phase I/II study were to determine the maximum tolerated dose (MTD) of LMB-100 when given with nanoalbumin bound (nab)-paclitaxel to participants with previously treated advanced pancreatic adenocarcinoma and to assess the objective response rate. Patients and Methods: Patients (n = 20) received fixed-dose nab-paclitaxel (125 mg/m2 on Days 1 and 8) with LMB-100 (65 or 100 mcg/kg on Days 1, 3, and 5) in 21-day cycles. Treatment was limited to 2-3 cycles by protocol. Safety and tolerability, pharmacokinetics, immunogenicity, and relationship of activity to tumor mesothelin expression were assessed. Results: Dose-limiting toxicity (DLT) of Grade 3 myalgia was observed in 2 of 5 patients treated with 100 mcg/kg. DLT of Grade 3 edema from capillary leak syndrome (CLS) was observed in 1 of 6 patients at MTD of 65 mcg/kg. Severe toxicities of Grade 4 left ventricular dysfunction and hypotension from CLS were observed in 1 patient in the phase II expansion, resulting in study closure. LMB-100 anti-drug antibody formation limited LMB-100 exposure in 5 of 13 patients during cycle 2. Seven of 17 patients with evaluable CA19-9 experienced >50% decrease of this tumor marker, and one patient developed a partial response. Response was associated with higher tumor mesothelin expression and Cycle 2 LMB-100 exposure. Conclusions: The combination caused serious toxicity. Despite some observed clinical activity, further testing of this combination will not be pursued. This abstract is also being presented as Poster B01. Citation Format: Christine C. Alewine, Mehwish Ahmad, Cody J. Peer, Zishuo Hu, Min-jung Lee, Akiro Yuno, Jessica Kindrick, Anish Thomas, Seth Steinberg, Jane B. Trepel, William D. Figg, Raffit Hassan, Ira Pastan. Phase I/II study of mesothelin-targeted immunotoxin LMB-100 with nab-paclitaxel for patients with advanced pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr PR07.