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

Research output: Contribution to journalArticle

24 Scopus citations

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 %.

Original languageEnglish (US)
Pages (from-to)467-473
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume73
Issue number3
DOIs
StatePublished - Mar 2014

Keywords

  • IGF-R1
  • Monoclonal antibody
  • Oncology regimens
  • Phase 1
  • R1507
  • Solid Tumor

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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    Mahadevan, D., Sutton, G. R., Arteta-Bulos, R., Bowden, C. J., Miller, P. J. E., Swart, R. E., Walker, M. S., Haluska, P., Munster, P. N., Marshall, J., Hamid, O., & Kurzrock, R. (2014). 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 chemotherapy and pharmacology, 73(3), 467-473. https://doi.org/10.1007/s00280-013-2372-x