Phase IA/II, multicentre, open-label study of the CD40 antagonistic monoclonal antibody lucatumumab in adult patients with advanced non-Hodgkin or Hodgkin lymphoma.
Despite advancements in the treatment of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL), patients continue to relapse and thus a need for new targeted therapies remains. The CD40 receptor is highly expressed on neoplastic B cells and activation leads to enhanced proliferation and survival. Lucatumumab (HCD122) is a fully human antagonistic CD40 monoclonal antibody. A phase IA/II study was designed to determine the maximum tolerated dose (MTD) and activity of lucatumumab in patients with relapsed/refractory lymphoma. Determination of the MTD was the primary objective of the phase IA dose escalation portion and clinical response was the primary objective of the phase II dose expansion portion. Patients received escalating doses of lucatumumab administered intravenously once weekly for 4 weeks of an 8-week cycle. MTD was determined at 4 mg/kg of lucatumumab. A total of 111 patients with NHL (n = 74) and HL (n = 37) were enrolled. Responses were observed across various lymphoma subtypes. The overall response rate by computed tomography among patients with follicular lymphoma (FL) and marginal zone lymphoma of mucosa-associated lymphatic tissue (MZL/MALT) was 33·3% and 42·9%, respectively. Lucatumumab demonstrates modest activity in relapsed/refractory patients with advanced lymphoma, suggesting that targeting of CD40 warrants further investigation.
University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michelle
M
Fanale
Sarit
S
Assouline
John
J
Kuruvilla
Philippe
P
Solal-Céligny
Dae S
DS
Heo
Gregor
G
Verhoef
Paolo
P
Corradini
Jeremy S
JS
Abramson
Fritz
F
Offner
Andreas
A
Engert
Martin J S
MJ
Dyer
Daniel
D
Carreon
Brett
B
Ewald
Johan
J
Baeck
Anas
A
Younes
Arnold S
AS
Freedman
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000037:antagonists & inhibitors*; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome; D055815:Young Adult
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D019013:CD40 Antigens; C578314:lucatumumab
Hodgkin lymphoma; monoclonal antibodies; non-Hodgkin lymphoma