A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis

Robert J. Arceci, Carl E. Allen, Ira J. Dunkel, Eric Jacobsen, James Whitlock, Robert Vassallo, Shannon R. Morris, Alison Portnoy, Beth Ann Reedy, Deborah A. Smith, Robert Noble, Amy Murnane, Mark Cornfeld, Carlos Rodriguez-Galindo, Mark L. Heaney, Kenneth Mcclain, Sarah Vaiselbuh

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Langerhans cell histiocytosis (LCH) is a clonal neoplasm characterized by widely varied clinical presentations, including multisystem involvement and systemic inflammatory symptoms. The AKT pathway is relevant to survival and proliferation of dendritic cells, and is also often upregulated in hematopoietic malignancies. A clinical response in an adult patient with LCH participating in the first-in-human trial of afuresertib prompted this prospective trial. Procedure: The population in the current study included treatment-naïve (n = 7) and recurrent/refractory patients with LCH (n = 10), who received oral afuresertib (125 mg). The majority of patients were treated for > 24 weeks, with four patients receiving treatment for > 48 weeks. Results: Pharmacokinetic analysis showed similar exposures in previously reported patients with other hematologic malignancies. Primary drug-related toxicities included Grade 1/2 nausea, diarrhea, dyspepsia, and vomiting. Grade 3 toxicities included fatigue, diarrhea, and pain (one of each). Another severe adverse event involved soft tissue necrosis. The overall response rate in evaluable subjects was 33% in treatment-naïve patients and 28% in patients with recurrent/refractory disease, which did not meet the predefined Bayesian criteria for efficacy. Conclusion: Afuresertib has clinical activity in some patients with newly diagnosed and advanced LCH.

Original languageEnglish (US)
JournalPediatric Blood and Cancer
DOIs
StateAccepted/In press - 2016

Fingerprint

Langerhans Cell Histiocytosis
Hematologic Neoplasms
Diarrhea
afuresertib
Dyspepsia
Drug-Related Side Effects and Adverse Reactions
Dendritic Cells
Nausea
Vomiting
Fatigue
Necrosis
Therapeutics
Pharmacokinetics
Pain
Survival

Keywords

  • Afuresertib
  • AKT inhibitor
  • Langerhans cell histiocytosis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis. / Arceci, Robert J.; Allen, Carl E.; Dunkel, Ira J.; Jacobsen, Eric; Whitlock, James; Vassallo, Robert; Morris, Shannon R.; Portnoy, Alison; Reedy, Beth Ann; Smith, Deborah A.; Noble, Robert; Murnane, Amy; Cornfeld, Mark; Rodriguez-Galindo, Carlos; Heaney, Mark L.; Mcclain, Kenneth; Vaiselbuh, Sarah.

In: Pediatric Blood and Cancer, 2016.

Research output: Contribution to journalArticle

Arceci, RJ, Allen, CE, Dunkel, IJ, Jacobsen, E, Whitlock, J, Vassallo, R, Morris, SR, Portnoy, A, Reedy, BA, Smith, DA, Noble, R, Murnane, A, Cornfeld, M, Rodriguez-Galindo, C, Heaney, ML, Mcclain, K & Vaiselbuh, S 2016, 'A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis', Pediatric Blood and Cancer. https://doi.org/10.1002/pbc.26325
Arceci, Robert J. ; Allen, Carl E. ; Dunkel, Ira J. ; Jacobsen, Eric ; Whitlock, James ; Vassallo, Robert ; Morris, Shannon R. ; Portnoy, Alison ; Reedy, Beth Ann ; Smith, Deborah A. ; Noble, Robert ; Murnane, Amy ; Cornfeld, Mark ; Rodriguez-Galindo, Carlos ; Heaney, Mark L. ; Mcclain, Kenneth ; Vaiselbuh, Sarah. / A phase IIa study of afuresertib, an oral pan-AKT inhibitor, in patients with Langerhans cell histiocytosis. In: Pediatric Blood and Cancer. 2016.
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AU - Allen, Carl E.

AU - Dunkel, Ira J.

AU - Jacobsen, Eric

AU - Whitlock, James

AU - Vassallo, Robert

AU - Morris, Shannon R.

AU - Portnoy, Alison

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AU - Smith, Deborah A.

AU - Noble, Robert

AU - Murnane, Amy

AU - Cornfeld, Mark

AU - Rodriguez-Galindo, Carlos

AU - Heaney, Mark L.

AU - Mcclain, Kenneth

AU - Vaiselbuh, Sarah

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