title: First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity.
abstract: BACKGROUND
  IMP321 is a recombinant soluble LAG-3Ig fusion protein that binds to MHC class II with high avidity and mediates APC and then antigen-experienced memory CD8+ T cell activation. We report clinical and biological results of a phase I/II in patients with metastatic breast carcinoma (MBC) receiving first-line paclitaxel weekly, 3 weeks out of 4.
  
  
  METHODS
  MBC patients were administered one dose of IMP321 s.c. every two weeks for a total of 24 weeks (12 injections). The repeated single doses were administered the day after chemotherapy at D2 and D16 of the 28-day cycles of paclitaxel (80 mg/m2 at D1, D8 and D15, for 6 cycles). Blood samples were taken 13 days after the sixth and the twelfth IMP321 injections to determine sustained APC, NK and memory CD8 T cell responses.
  
  
  RESULTS
  Thirty MBC patients received IMP321 in three cohorts (doses: 0.25, 1.25 and 6.25 mg). IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells. Clinical benefit was observed for 90% of patients with only 3 progressors at 6 months. Also, the objective tumor response rate of 50% compared favorably to the 25% rate reported in the historical control group.
  
  
  CONCLUSIONS
  The absence of toxicity and the demonstration of activity strongly support the future development of this agent for clinical use in combined first-line regimens.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00349934.
authors.affiliation: Immutep SA, 2 rue Jean Rostand, Orsay 91893, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Brignone
authors.forename: Maya
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Fawzia
authors.initials: F
authors.lastname: Mefti
authors.forename: Etienne
authors.initials: E
authors.lastname: Brain
authors.forename: Rosana
authors.initials: R
authors.lastname: Jarcau
authors.forename: Frédérique
authors.initials: F
authors.lastname: Cvitkovic
authors.forename: Nabil
authors.initials: N
authors.lastname: Bousetta
authors.forename: Jacques
authors.initials: J
authors.lastname: Medioni
authors.forename: Joseph
authors.initials: J
authors.lastname: Gligorov
authors.forename: Caroline
authors.initials: C
authors.lastname: Grygar
authors.forename: Manon
authors.initials: M
authors.lastname: Marcu
authors.forename: Frédéric
authors.initials: F
authors.lastname: Triebel
mesh_terms: D000368:Aged; D000912:Antibodies, Neoplasm / Q000276:immunology; D015703:Antigens, CD / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D002452:Cell Count; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012074:Remission Induction; D016896:Treatment Outcome; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000970:Antineoplastic Agents; D017239:Paclitaxel; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human