| General information |
| Database: | DB00691 |
| Objective: | Thisphase 1b doseescalation study assessed safety, tolerability, and pharmacokinetics of ganitumab, a fully human monoclonal antibody against the insulinlike growth factor 1 (IGF1) receptor, combined with targeted agents or cytotoxic chemotherapy in patients with advanced solid tumors. |
| Authors: | Rosen LS, et al |
| Title: | Safety and pharmacokinetics of ganitumab (AMG 479) combined with sorafenib, panitumumab, erlotinib, or gemcitabine in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22510349 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | ganitumab
|
| Target: | Insulinlike growth factor I receptor
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 7 |
| Therapeutic Combination Content: | ganitumab (AMG 479) combined with sorafenib, panitumumab, erlotinib, or gemcitabine |
| Study Type: | phase Ib doseescalation study |
| Key Patients Feature: | Patients aged 18 years or more with pathologically orcytologically documented advanced solid tumors or renalcell carcinoma (sorafenib cohorts) refractory to at least 1line of therapy or for which no standard or curative therapywas available; measurable or evaluable disease per WorldHealth Organization (WHO) guidelines; an Eastern Cooperative Oncology Group performance status of 2 or less; lifeexpectancy of 3 months or more; and adequate hematologic, renal, and hepatic function were eligible to enroll. |
| Biomarker: | Circulating total IGF1 and IGF binding protein 3 |
| Biomark Analysis: | Circulating total IGF1 and IGF binding protein 3 increased from baseline following treatment. |
| Control Group Info: | single arm |
| Treatment Info: | Patients with treatmentrefractory advanced solid tumors were sequentially enrolled at 2 ganitumab dose levels (6 or 12 mg/kg i.v. every 2 weeks) combined with either sorafenib 400 mg twice daily, panitumumab 6 mg/kg every 2 weeks, erlotinib 150 mg once daily, or gemcitabine 1, 000 mg/m(2) on days 1, 8, and 15 of each 4week cycle. |
| Primary End Point: | safety and pharmacokinetics |
| Secondary End Point: | NA |
| Patients Number: | 24 |
| Trial Results |
| DLT_MTD: | Ganitumab up to 12 mg/kg appeared well tolerated combined with sorafenib, panitumumab, erlotinib, or gemcitabine. |
| Objective Response Rate: | Four patients (9%) had partial responses. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Treatmentemergent adverse events were generally mild and included fatigue, nausea, vomiting, and chills. Three patients had doselimiting toxicities: grade 3 hyperglycemia (ganitumab 6 mg/kg and panitumumab), grade 4 neutropenia (ganitumab 6 mg/kg and gemcitabine), and grade 4 thrombocytopenia (ganitumab 12 mg/kg and erlotinib). |
| Conclusions: | Ganitumab up to 12 mgkg was well tolerated, without adverse effects on pharmacokinetics in combination with either sorafenib, panitumumab, erlotinib, or gemcitabine. Ganitumab is currently under investigation in combination with some of these and other agents. |