title: Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR™ therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients.
abstract: OBJECTIVE
  CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic that triggers direct caspase independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. This study evaluated the safety, pharmacokinetics, and efficacy of otlertuzumab administered in combination with rituximab and bendamustine to patients with relapsed, indolent B-cell non-Hodgkin Lymphoma (NHL).
  
  
  METHODS
  Patients with relapsed or refractory NHL received otlertuzumab (10 or 20 mg/kg) intravenously (IV) on days 1 and 15, bendamustine (90 mg/m(2)) on days 1 and 2, and rituximab (375 mg/m(2)) on day 1 for up to six 28 day cycles. Responses were determined using standard criteria.
  
  
  RESULTS
  Twelve patients were treated with 6 patients at each dose level; median age was 57 years (range, 51-79), and median number of prior regimens was 3 (range, 1-4). All patients had relapsed after prior rituximab including 7 refractory to their most recent previous treatment. In the 10 and 20 mg/kg dose cohorts, the mean half-life was 8 and 10 days following the first dose, and 12 or 14 days following 12 doses of otlertuzumab, respectively. Overall response rate was 83% (10/12) with 4 CRs (32%). The most frequent adverse events were neutropenia, nausea, fatigue, leukopenia, and insomnia; most were grade 1 or 2.
  
  
  CONCLUSIONS
  Otlertuzumab in combination with rituximab and bendamustine was well tolerated and induced responses in the majority of patients with relapsed indolent B-NHL. NCI Clinical Trials Network registration: NCT01317901.
authors.affiliation: Department of Medicine, University of Washington, Box 358081, 825 Eastlake Ave E.,, MS G3200, Seattle, WA, USA, agopal@u.washington.edu.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.forename: Stefano R
authors.initials: SR
authors.lastname: Tarantolo
authors.forename: Naresh
authors.initials: N
authors.lastname: Bellam
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.forename: Melissa
authors.initials: M
authors.lastname: Griffin
authors.forename: Tatyana
authors.initials: T
authors.lastname: Feldman
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Mato
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eisenfeld
authors.forename: Scott C
authors.initials: SC
authors.lastname: Stromatt
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000951:Antigens, Neoplasm; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000069283:Rituximab; D059470:Tetraspanins / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; D007074:Immunoglobulin G; D009588:Nitrogen Mustard Compounds; D011993:Recombinant Fusion Proteins; C547387:TRU 016; D059470:Tetraspanins; D000069283:Rituximab; D000069461:Bendamustine Hydrochloride