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Ref Type Journal Article
PMID (31792036)
Authors Alewine C, Ahmad M, Peer CJ, Hu ZI, Lee MJ, Yuno A, Kindrick JD, Thomas A, Steinberg SM, Trepel JB, Figg WD, Hassan R, Pastan I
Title Phase I/II Study of the Mesothelin-targeted Immunotoxin LMB-100 with Nab-Paclitaxel for Patients with Advanced Pancreatic Adenocarcinoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 26
Issue 4
Date 2020 Feb 15
URL
Abstract Text 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 (n = 20) received fixed-dose nab-paclitaxel (125 mg/m2 on days 1 and 8) with LMB-100 (65 or 100 μg/kg on days 1, 3, and 5) in 21-day cycles for 1-3 cycles.Fourteen patients were treated on the dose escalation and an additional six in the phase II expansion. MTD of 65 μg/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 μg/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.Although clinical activity was observed, the combination was not well tolerated and alternative drug combinations with LMB-100 will be pursued.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown pancreatic ductal adenocarcinoma not applicable LMB-100 + Nab-paclitaxel Phase Ib/II Actionable In a Phase I/II trial, the combination of LMB-100 and Abraxane (nab-paclitaxel) led to a greater than 50% decrease in CA19-9 in 41% (7/17) of patients with pancreatic ductal adenocarcinoma, and one patient experienced an objective partial response, however, the combination therapy was not well tolerated (PMID: 31792036; NCT02810418). 31792036