In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e13574-e13574
Abstract:
e13574 Background: R1507 is a human IgG1 Mab that binds to the insulin-like growth factor-1 receptor (IGF-1R), implicated in the pathogenesis of several solid tumor types. IGF-1 or IGF-2 activate the IGF-1R and promote anchorage independent growth of malignant cells. A phase 1b study was conducted to establish the safety, tolerability and efficacy of R1507 in combination with multiple standard oncology regimens. Methods: This was an open-label, multi-center study in advanced stage cancer patients (pts). R1507 (3, 5, 9, 10 and 16 mg/kg IV, Q2W or Q3W) was added to 6 treatment regimens: gemcitabine + erlotinib (GE); paclitaxel + bevacizumab (PB); carboplatin + etoposide (CE); mFOLFOX6 + bevacizumab (FB); capecitabine + trastuzumab (CT); sorafenib (S). All arms started with R1507 dose lower than the recommended single agent dose (level -1). If tolerable, R1507 dose was escalated in subsequent cohorts of pts. Accrual to each regimen was dependent on the number of pts developing a DLT at dose level -1. The study used a 3 + 3 + 6 and a 3 + 9 design. Results: N=104 pts enrolled into regimens 1 to 6: 6% new diagnosis, 93% non-recent diagnosis, and 1% not classified. N=18 withdrew for safety [1 death, 17 AEs]. N=80 withdrew for non-safety reasons [n=61 PD, n=17 refused further treatment, n=1 insufficient response, n=1 ‘other’] . A total of 1337 AEs were reported: any grade, across regimens and doses were nausea, diarrhea, and vomiting. N=123 had grade ≥3 AEs (n=28 dose level -1; n=95 dose level 1) in 60 pts that were myelosuppression, fatigue and mucosal inflammation. ORR (partial response [PR] plus stable disease) of evaluable pts across 6 regimens was 36% with 5 PRs: regimens PB (non-small cell lung cancer, nasopharyngeal cancer), CE (melanoma), FB (colon cancer) and S (gastrointestinal stromal tumor: GIST). The GIST pt ( 〉 4 prior therapies) had a PR for 3 years. Three pts (breast cancer, melanoma, adenoid cystic carcinoma) were on study for 〉 1 year. 71% pts had SD ≥ 4 months. Conclusions: R1507 added to 6 standard chemotherapy regimens was well tolerated with no significant safety issues. Trial was terminated early due to discontinued development of R1507. Clinical trial information: NCT00811993.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.e13574
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
