| General information |
| Database: | DB00812 |
| Objective: | HER3 is a key dimerization partner for other HER family members, and its expression is associated with poor prognosis. This firstinhuman study of U31287 (NCT00730470), a fully human antiHER3 monoclonal antibody, evaluated its safety, tolerability, and pharmacokinetics in patients with advanced solid tumor. |
| Authors: | LoRusso P, et al |
| Title: | Phase I study of U31287, a fully human antiHER3 monoclonal antibody, in patients with advanced solid tumors. |
| Journal: | Clin Cancer Res. |
| Year: | 2013 |
| PMID: | 23591447 |
| Trial Design |
| Clinical Trial Id: | NCT00730470 |
| Agent: | U31287
|
| Target: | Receptor proteintyrosine kinase erbB3
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase I study |
| Key Patients Feature: | patients with advanced solid tumors |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The study was conducted in 2 parts: part 1sequential cohorts received escalating doses (0.320 mg/kg) of U31287 every 2 weeks, starting 3 weeks after the first dose; part 2additional patients received 9, 14, or 20 mg/kg U31287 every 2 weeks, based on observed tolerability and pharmacokinetics from part 1. |
| Primary End Point: | Recommended phase II dose, adverse event rates, pharmacokinetics, and tumor response were determined. |
| Secondary End Point: | NA |
| Patients Number: | 47 |
| Trial Results |
| DLT_MTD: | DLT was defined as drugrelated grade 3 or higher hematologic or nonhematologic toxicity (except alopecia); for fatigue, only grade 3 fatigue that persisted for more than 7 days or grade 4 fatigue of any length was included. MTD was defined as the highest dose with an observed incidence of DLT in less than 33% of the patients in the cohort. |
| Objective Response Rate: | NA |
| 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): | The most common adverse events overall (more than and equal to 20% of patients) included fatigue (42.1%), diarrhea (24.6%), nausea (22.8%), and dyspnea (21.1%) |
| Conclusions: | U31287 treatment was well tolerated, and some evidence of disease stabilization was observed. Pharmacokinetic data support U31287 dosing of 9 to 20 mgkg every 2 to 3 weeks. Combination studies of U31287 are ongoing. |