PMID- 24390424
OWN - NLM
STAT- MEDLINE
DCOM- 20140710
LR  - 20191210
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 73
IP  - 3
DP  - 2014 Mar
TI  - 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.
PG  - 467-73
LID - 10.1007/s00280-013-2372-x [doi]
AB  - 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 %.
FAU - Mahadevan, Daruka
AU  - Mahadevan D
AD  - The University of Tennessee/West Clinic, 100 North Humphreys Blvd., Memphis, TN, 
      38120, USA, dmahadevan@westclinic.com.
FAU - Sutton, Gregory Ryan
AU  - Sutton GR
FAU - Arteta-Bulos, Rafael
AU  - Arteta-Bulos R
FAU - Bowden, Chris J
AU  - Bowden CJ
FAU - Miller, Paul J E
AU  - Miller PJ
FAU - Swart, Rachel Elizabeth
AU  - Swart RE
FAU - Walker, Mark S
AU  - Walker MS
FAU - Haluska, Paul
AU  - Haluska P
FAU - Munster, Pamela N
AU  - Munster PN
FAU - Marshall, John
AU  - Marshall J
FAU - Hamid, Omid
AU  - Hamid O
FAU - Kurzrock, Razelle
AU  - Kurzrock R
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
DEP - 20140104
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - Y64GQ0KC0A (teprotumumab)
SB  - IM
MH  - Administration, Intravenous
MH  - Antibodies, Monoclonal/*administration & dosage/*adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/*adverse 
      effects
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neoplasms/*drug therapy/immunology
MH  - Receptor, IGF Type 1/immunology
EDAT- 2014/01/07 06:00
MHDA- 2014/07/11 06:00
CRDT- 2014/01/07 06:00
PHST- 2013/08/21 00:00 [received]
PHST- 2013/12/19 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/07/11 06:00 [medline]
AID - 10.1007/s00280-013-2372-x [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2014 Mar;73(3):467-73. doi: 
      10.1007/s00280-013-2372-x. Epub 2014 Jan 4.