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

  • Daruka Mahadevan
  • Gregory Ryan Sutton
  • Rafael Arteta-Bulos
  • Chris J. Bowden
  • Paul J. E. Miller
  • Rachel Elizabeth Swart
  • Mark S. Walker
  • Paul Haluska
  • Pamela N. Munster
  • John Marshall
  • Omid Hamid
  • Razelle Kurzrock
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

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 %.

Keywords

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

Authors and Affiliations

  • Daruka Mahadevan
    • 1
  • Gregory Ryan Sutton
    • 1
  • Rafael Arteta-Bulos
    • 1
  • Chris J. Bowden
    • 2
  • Paul J. E. Miller
    • 3
  • Rachel Elizabeth Swart
    • 4
  • Mark S. Walker
    • 3
  • Paul Haluska
    • 5
  • Pamela N. Munster
    • 6
  • John Marshall
    • 7
  • Omid Hamid
    • 8
  • Razelle Kurzrock
    • 9
  1. 1.The University of Tennessee/West ClinicMemphisUSA
  2. 2.Genentech, Inc.San FranciscoUSA
  3. 3.ACORN ResearchLLCMemphisUSA
  4. 4.Arizona Oncology/USONTucsonUSA
  5. 5.Mayo ClinicRochesterUSA
  6. 6.University of California, San FranciscoSan FranciscoUSA
  7. 7.Georgetown University HospitalWashingtonUSA
  8. 8.The Angeles Clinic and Research InstituteSanta MonicaUSA
  9. 9.University of California, San DiegoSan DiegoUSA