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A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia.

Publication ,  Journal Article
Stein, EM; Walter, RB; Erba, HP; Fathi, AT; Advani, AS; Lancet, JE; Ravandi, F; Kovacsovics, T; DeAngelo, DJ; Bixby, D; Faderl, S; Ho, PA ...
Published in: Blood
January 25, 2018

Vadastuximab talirine (SGN-CD33A, 33A) is an antibody-drug conjugate consisting of pyrrolobenzodiazepine dimers linked to a monoclonal antibody targeting CD33, which is expressed in the majority of acute myeloid leukemia (AML) patients. This phase 1 study evaluated the safety, pharmacokinetics, and preliminary activity of vadastuximab talirine and determined the recommended monotherapy dose in patients with relapsed or refractory AML. Additional expansion cohorts tested vadastuximab talirine in specific subpopulations of relapsed AML, and in a cohort of older, treatment-naive patients. Patients received vadastuximab talirine IV on day 1 (5-60 µg/kg) or on days 1 and 4 (20 µg/kg) of 21-day cycles. A total of 131 patients (median age, 73 years [range, 26-89 years]) had intermediate I-II (48%) or adverse (34%) risk by European LeukemiaNet classification; 50% of patients had underlying myelodysplasia. Two dose-limiting toxicities (grade 2 pulmonary embolism and grade 4 hypocellular marrow) occurred during dose finding. Most adverse events (AEs) were consistent with myelosuppression; nonhematologic AEs included fatigue, nausea, and diarrhea. The 30-day mortality was 8%. At the recommended monotherapy dose of 40 µg/kg, the complete remission + CRi rate was 28% (5 of 18 patients); 50% of patients who responded achieved minimal residual disease negativity. In patients across dose levels who achieved CR or CRi, the median time to full count recovery was 6.4 weeks for neutrophils (≥1000/µL) and 10.6 weeks for platelets (≥100 × 109/L). Vadastuximab talirine demonstrates activity and a tolerable safety profile as a single agent in patients with AML. The recommended monotherapy dose of vadastuximab talirine is 40 µg/kg. This trial was registered at www.clinicaltrials.gov as # NCT01902329.

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

January 25, 2018

Volume

131

Issue

4

Start / End Page

387 / 396

Location

United States

Related Subject Headings

  • Sialic Acid Binding Ig-like Lectin 3
  • Pyrroles
  • Middle Aged
  • Male
  • Liver
  • Leukemia, Myeloid, Acute
  • Immunology
  • Immunoconjugates
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Stein, E. M., Walter, R. B., Erba, H. P., Fathi, A. T., Advani, A. S., Lancet, J. E., … Stein, A. S. (2018). A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood, 131(4), 387–396. https://doi.org/10.1182/blood-2017-06-789800
Stein, Eytan M., Roland B. Walter, Harry P. Erba, Amir T. Fathi, Anjali S. Advani, Jeffrey E. Lancet, Farhad Ravandi, et al. “A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia.Blood 131, no. 4 (January 25, 2018): 387–96. https://doi.org/10.1182/blood-2017-06-789800.
Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, et al. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood. 2018 Jan 25;131(4):387–96.
Stein, Eytan M., et al. “A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia.Blood, vol. 131, no. 4, Jan. 2018, pp. 387–96. Pubmed, doi:10.1182/blood-2017-06-789800.
Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, Ravandi F, Kovacsovics T, DeAngelo DJ, Bixby D, Faderl S, Jillella AP, Ho PA, O’Meara MM, Zhao B, Biddle-Snead C, Stein AS. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood. 2018 Jan 25;131(4):387–396.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

January 25, 2018

Volume

131

Issue

4

Start / End Page

387 / 396

Location

United States

Related Subject Headings

  • Sialic Acid Binding Ig-like Lectin 3
  • Pyrroles
  • Middle Aged
  • Male
  • Liver
  • Leukemia, Myeloid, Acute
  • Immunology
  • Immunoconjugates
  • Humans
  • Female