Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 3, pp 467–473

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


    • The University of Tennessee/West Clinic
  • Gregory Ryan Sutton
    • The University of Tennessee/West Clinic
  • Rafael Arteta-Bulos
    • The University of Tennessee/West Clinic
  • Chris J. Bowden
    • Genentech, Inc.
  • Paul J. E. Miller
    • ACORN ResearchLLC
  • Rachel Elizabeth Swart
    • Arizona Oncology/USON
  • Mark S. Walker
    • ACORN ResearchLLC
  • Paul Haluska
    • Mayo Clinic
  • Pamela N. Munster
    • University of California, San Francisco
  • John Marshall
    • Georgetown University Hospital
  • Omid Hamid
    • The Angeles Clinic and Research Institute
  • Razelle Kurzrock
    • University of California, San Diego
Original Article

DOI: 10.1007/s00280-013-2372-x

Cite this article as:
Mahadevan, D., Sutton, G.R., Arteta-Bulos, R. et al. Cancer Chemother Pharmacol (2014) 73: 467. doi:10.1007/s00280-013-2372-x



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.


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.


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.


R1507 added to six standard oncology regimens was well tolerated with an ORR of 36 %.


Solid TumorPhase 1IGF-R1R1507Oncology regimensMonoclonal antibody

Supplementary material

280_2013_2372_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014