Safety, Tolerability, and Preliminary Activity of LB-100, an Inhibitor of Protein Phosphatase 2A, in Patients with Relapsed Solid Tumors: An Open-Label, Dose Escalation, First-in-Human, Phase I Trial

Clin Cancer Res. 2017 Jul 1;23(13):3277-3284. doi: 10.1158/1078-0432.CCR-16-2299. Epub 2016 Dec 30.


Purpose: To determine the MTD and to assess the safety, tolerability, and potential activity of LB-100, a first-in-class small-molecule inhibitor of protein phosphatase 2A (PP2A) in adult patients with progressive solid tumors.Experimental Design: LB-100 was administered intravenously daily for 3 days in 21-day cycles in a 3 + 3 dose escalation design.Results: There were 29 patient entries over 7 dose escalations. One patient stopped treatment after one dose because of an acute infection and was reenrolled after recovery; each course was analyzed as a separate patient entry. Two patients had dose-limiting toxicity (reversible increases in serum creatinine or calculated serum creatinine clearance) at the 3.1 mg/m2 level. Probable or possible study drug-related grade 3 adverse events occurred in 6 (20.7%) patients [anemia (n = 2), decreased creatinine clearance, dyspnea, hyponatremia, and lymphopenia]. Ten (50%) of 20 response-evaluable patients had stable disease for four or more cycles. One patient with pancreatic adenocarcinoma had a partial response noted after 10 cycles, which was maintained for five additional cycles. The other patients achieving stable disease had one of the following: fibrosarcoma, chondrosarcoma, thymoma, atypical carcinoid of lung, or ovarian, testicular, breast (n = 2), and prostate cancer. The recommended phase II dose of LB-100 is 2.33 mg/m2 daily for 3 days every 3 weeks.Conclusions: The safety, tolerability, preliminary evidence of antitumor activity, and novel mechanism of action of LB-100 support its continued development alone and in combination with other therapies. Clin Cancer Res; 23(13); 3277-84. ©2016 AACR.

MeSH terms

  • Adult
  • Aged
  • Bridged Bicyclo Compounds, Heterocyclic / administration & dosage*
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug-Related Side Effects and Adverse Reactions / classification
  • Drug-Related Side Effects and Adverse Reactions / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Protein Phosphatase 2 / antagonists & inhibitors*
  • Protein Phosphatase 2 / genetics


  • Bridged Bicyclo Compounds, Heterocyclic
  • LB100
  • Piperazines
  • Protein Phosphatase 2