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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

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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 %.

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Acknowledgments

We wish to thank Roche Pharmaceuticals for supporting this trial, clinical research coordinators, research nurses and patients and their families for participating in this trial. We wish to thank Elizabeth Claire Dees, M.D., University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA and Michael L. Maitland, M.D., University of Chicago Medicine, Chicago, IL, USA for their participation in this trial.

Author information

Authors and Affiliations

  1. The University of Tennessee/West Clinic, 100 North Humphreys Blvd., Memphis, TN, 38120, USA

    Daruka Mahadevan, Gregory Ryan Sutton & Rafael Arteta-Bulos

  2. Genentech, Inc., San Francisco, CA, USA

    Chris J. Bowden

  3. ACORN Research, LLC, Memphis, TN, USA

    Paul J. E. Miller & Mark S. Walker

  4. Arizona Oncology/USON, Tucson, AZ, USA

    Rachel Elizabeth Swart

  5. Mayo Clinic, Rochester, MN, USA

    Paul Haluska

  6. University of California, San Francisco, San Francisco, CA, USA

    Pamela N. Munster

  7. Georgetown University Hospital, Washington, DC, USA

    John Marshall

  8. The Angeles Clinic and Research Institute, Santa Monica, CA, USA

    Omid Hamid

  9. University of California, San Diego, San Diego, CA, USA

    Razelle Kurzrock

Authors
  1. Daruka Mahadevan
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  2. Gregory Ryan Sutton
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  3. Rafael Arteta-Bulos
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Corresponding author

Correspondence to Daruka Mahadevan.

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Mahadevan, D., Sutton, G.R., Arteta-Bulos, R. et al. 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. Cancer Chemother Pharmacol 73, 467–473 (2014). https://doi.org/10.1007/s00280-013-2372-x

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  • DOI: https://doi.org/10.1007/s00280-013-2372-x

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