title: Phase 1b study of safety, tolerability and efficacy of R1507, a monoclonal antibody to IGF-1R in combination with multiple standard oncology regimens in patients with advanced solid malignancies.
abstract: BACKGROUND
  R1507 is a human IgG1 Mab that binds to the insulin-like growth factor-1 receptor (IGF-1R) and inhibits IGF-1- or IGF-2-mediated anchorage-independent growth of malignant cells. A phase 1b study evaluated the safety, tolerability and efficacy of R1507 in combination with multiple standard oncology regimens.
  
  
  METHODS
  R1507 (3, 5, 9, 10 and 16 mg/kg IV, Q2 W or Q3 W) was added to six treatment regimens: gemcitabine + erlotinib (GE); paclitaxel + bevacizumab (PB); carboplatin + etoposide (CE); mFOLFOX6 + bevacizumab (FB); capecitabine + trastuzumab (CT); and sorafenib (S). If tolerable, R1507 dose was escalated utilizing a 3 + 3 + 6 and a 3 + 9 design.
  
  
  RESULTS
  A total of 104 patients enrolled into regimens 1-6: 93 % were non-recent diagnoses. Eighteen withdrew for safety [one death, 17 adverse events (AEs)]. A total of 1,337 AEs any grade, across regimens and doses were nausea, vomiting and diarrhea. A total of 123 had grade ≥3 AEs (n = 28 dose level 1; n = 95 dose level 1) and in 60 patients were myelosuppression, fatigue and mucosal inflammation. ORR (PR plus SD) of evaluable patients across six regimens was 36 % with five PRs: regimens PB (non-small cell lung cancer, nasopharyngeal cancer), CE (melanoma), FB (colon cancer) and S (GIST). The GIST pt (>4 prior therapies) had a PR for 3 years. Three patients (breast cancer, melanoma and adenoid cystic carcinoma) were on study for >1 year; 76 % of patients had SD or better for 4 months.
  
  
  CONCLUSIONS
  R1507 added to six standard oncology regimens was well tolerated with an ORR of 36 %.
authors.affiliation: The University of Tennessee/West Clinic, 100 North Humphreys Blvd., Memphis, TN, 38120, USA, dmahadevan@westclinic.com.
authors.forename: Daruka
authors.initials: D
authors.lastname: Mahadevan
authors.forename: Gregory Ryan
authors.initials: GR
authors.lastname: Sutton
authors.forename: Rafael
authors.initials: R
authors.lastname: Arteta-Bulos
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Bowden
authors.forename: Paul J E
authors.initials: PJ
authors.lastname: Miller
authors.forename: Rachel Elizabeth
authors.initials: RE
authors.lastname: Swart
authors.forename: Mark S
authors.initials: MS
authors.lastname: Walker
authors.forename: Paul
authors.initials: P
authors.lastname: Haluska
authors.forename: Pamela N
authors.initials: PN
authors.lastname: Munster
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Omid
authors.initials: O
authors.lastname: Hamid
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D061605:Administration, Intravenous; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017526:Receptor, IGF Type 1 / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017526:Receptor, IGF Type 1; C551399:teprotumumab