Nivolumab Exposure-Response Analyses of Efficacy and Safety in Previously Treated Squamous or Nonsquamous Non-Small Cell Lung Cancer.

Nivolumab is a fully human IgG4 monoclonal antiprogrammed death-1 antibody with demonstrated efficacy, including durable responses and prolonged survival, in patients with previously treated, advanced non-small cell lung cancer (NSCLC). Exposure-response (E-R) analyses for efficacy and safety were conducted to inform the benefit-risk assessment of nivolumab in this patient population. The analyses used clinical trial data from patients with squamous ( = 293) or nonsquamous ( = 354) NSCLC from four clinical trials who received nivolumab doses of 1 to 10 mg/kg every 2 weeks.

IRS2 copy number gain, KRAS and BRAF mutation status as predictive biomarkers for response to the IGF-1R/IR inhibitor BMS-754807 in colorectal cancer cell lines.

Insulin-like growth factor receptor 1 (IGF-1R)-targeting therapies are currently at an important crossroad given the low clinical response rates seen in unselected patients. Predictive biomarkers for patient selection are critical for improving clinical benefit. Coupling in vitro sensitivity testing of BMS-754807, a dual IGF-1R/IR inhibitor, with genomic interrogations in 60 human colorectal cancer cell lines, we identified biomarkers correlated with response to BMS-754807.

Dual IGF-1R/InsR inhibitor BMS-754807 synergizes with hormonal agents in treatment of estrogen-dependent breast cancer.

Insulin-like growth factor (IGF) signaling has been implicated in the resistance to hormonal therapy in breast cancer. Using a model of postmenopausal, estrogen-dependent breast cancer, we investigated the antitumor effects of the dual IGF-1R/InsR tyrosine kinase inhibitor BMS-754807 alone and in combination with letrozole or tamoxifen. BMS-754807 exhibited antiproliferative effects in vitro that synergized strongly in combination with letrozole or 4-hydroxytamoxifen and fulvestrant.

Dual inhibition of the epidermal growth factor receptor pathway with cetuximab and erlotinib: a phase I study in patients with advanced solid malignancies.

Purpose: To determine the optimal dose of the antiepidermal growth factor receptor (EGFR) monoclonal antibody cetuximab that can be safely administered in combination with a standard daily dose of erlotinib in patients with advanced solid malignancies.

Patients And Methods: Patients with advanced solid malignancies who had failed standard chemotherapies received escalating doses of cetuximab without a loading dose (100, 200, 250 mg/m(2) i.v.

Molecular classification of rhabdomyosarcoma--genotypic and phenotypic determinants of diagnosis: a report from the Children's Oncology Group.

Rhabdomyosarcoma (RMS) in children occurs as two major histological subtypes, embryonal (ERMS) and alveolar (ARMS). ERMS is associated with an 11p15.5 loss of heterozygosity (LOH) and may be confused with nonmyogenic, non-RMS soft tissue sarcomas.