Table 1.

Phase 1 studies of CD40-targeted therapy in cancer patients

DrugFormulationCD40 signalingPatient populationClinical trial findingsReference
Recombinant CD40LRecombinant human trimerAgonistSolid tumors or NHL (n = 32)• Increased AST/ALTVonderheide et al. (46)
• Injection site reactions
• 2 PR
CP-870,893Fully human IgG2 mAbAgonistSolid tumors (n = 29)• CRSVonderheide et al. (49)
• 4 PR
SGN-40Humanized IgG1 mAbWeak agonistNHL (n = 29; ongoing)• CRSForero-Torres et al. (53)
• 4 PR, 1 CR
Multiple myeloma (n = 23; ongoing)• CRSHussein et al. (54)
• 4 patients with decreases in M-protein
HCD 122Fully human IgG1 mAbAntagonistCLL and multiple myelomaByrd et al. (77)*
Bensinger et al. (78)*
CD40L-expressing CLL cellsAdenovirus gene therapyAgonistCLL (n = 11)• Flu-like symptomsWierda et al. (57)
• Reductions in tumor burden
Leukemia cells with CD40L and IL-2–expressing fibroblastsAdenovirus gene therapyAgonistAcute or lymphoblastic leukemia in remission (n = 10)• Well toleratedRousseau et al. (58)
• 9 patients disease-free at median follow-up of 41 mo
  • Abbreviations: AST, aspartate aminotransferase; ALT, alanine aminotransferase; NHL, non–Hodgkin's lymphoma; PR, partial response; CR, complete response; CRS, cytokine release syndrome; CLL, chronic lymphocytic leukemia.

  • * See note added in proof.