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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Purpose: LMB-100 is a recombinant immunotoxin (iTox) consisting 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 objectives of this phase I/II study were to determine the MTD of LMB-100 when administered with nanoalbumin bound (nab)-paclitaxel to patients with previously treated advanced pancreatic adenocarcinoma and to assess the objective response rate. Patients and Methods: Patients (n ¼ 20) received fixed-dose nab-paclitaxel (125 mg/m2 on days 1 and 8) with LMB-100 (65 or 100 mg/kg on days 1, 3, and 5) in 21-day cycles for 1–3 cycles. Results: Fourteen patients were treated on the dose escalation and an additional six in the phase II expansion. MTD of 65 mg/kg was established for the combination. Dose-limiting toxicity resulting from capillary leak syndrome (CLS) was seen in two of five patients treated at 100 mg/kg and one of six evaluable phase I patients receiving the MTD. Severity of CLS was associated with increases in apoptotic circulating endothelial cells. LMB-100 exposure was unaffected by anti-LMB-100 antibody formation in five of 13 patients during cycle 2. Seven of 17 evaluable patients experienced >50% decrease in CA 19-9, including three with previous exposure to nab-paclitaxel. One patient developed an objective partial response. Patients with biomarker responses had higher tumor mesothelin expression. Conclusions: Although clinical activity was observed, the combination was not well tolerated and alternative drug combinations with LMB-100 will be pursued.

Original languageEnglish
Pages (from-to)828-836
Number of pages9
JournalClinical Cancer Research
Volume26
Issue number4
DOIs
StatePublished - Feb 15 2020

Fingerprint

Dive into the research topics of 'Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma'. Together they form a unique fingerprint.

Cite this