Faculty Collaboration Database

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 2014 Mar;73(3):467-73

Date

01/07/2014

Pubmed ID

24390424

DOI

10.1007/s00280-013-2372-x

Scopus ID

2-s2.0-84896040011 (requires institutional sign-in at Scopus site)   34 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 %.

Author List

Mahadevan D, Sutton GR, Arteta-Bulos R, Bowden CJ, Miller PJ, Swart RE, Walker MS, Haluska P, Munster PN, Marshall J, Hamid O, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Intravenous
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Female
Humans
Male
Middle Aged
Neoplasms
Receptor, IGF Type 1