| General information |
| Database: | DB00157 |
| Objective: | To evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of mapatumumab, a fully human monoclonal antibody targeting tumor necrosis factorrelated apoptosisinducing ligand receptor 1 (TRAILR1), in combination with gemcitabine and cisplatin. |
| Authors: | Mom CH, et al |
| Title: | Mapatumumab, a fully human agonistic monoclonal antibody that targets TRAILR1, in combination with gemcitabine and cisplatin: a phase I study. |
| Journal: | Clin Cancer Res |
| Year: | 2009 |
| PMID: | 19690193 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | mapatumumab
|
| Target: | Tumor necrosis factor receptor superfamily member 10A
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Mapatumumab+gemcitabine + cisplatin |
| Study Type: | a phase I Study |
| Key Patients Feature: | Patients with advanced solid tumors |
| Biomarker: | TRAILR1 expression |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | received gemcitabine 1, 250 mg/m(2) i.v. on days 1 and 8 and cisplatin 80 mg/m(2) i.v. on day 1 of each 21day cycle. Escalating mapatumumab doses were administered i.v. every 21 days. |
| Primary End Point: | to evaluate the safety and tolerability of escalating doses of mapatumumab+gemcitabine and cisplatin in patients with solid tumors. |
| Secondary End Point: | plasma mapatumumab concentrations, the influence of mapatumumab on plasma gemcitabine and cisplatin pharmacokinetics, disease response, and TRAILR1 expression. |
| Patients Number: | 49 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicities were seen in 3 of 12 patients at 10 mg/kg, consisting of grade 3 transaminitis, neutropenic fever, and grade 4 thrombocytopenia. At 20 mg/kg, 2 of 12 patients had doselimiting toxicities, including grade 4 thrombocytopenia and grade 4 fatigue. The maximum tolerated dose was not reached. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Ttheylve patients had a partial response, and 25 patients showed stable disease with a median duration of 6 months. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The adverse events most commonly observed reflect the toxicity profile of gemcitabine and cisplatin. |
| Conclusions: | Mapatumumab in combination with gemcitabine and cisplatin is safe and well tolerated at doses up to 30 mgkg. Further studies on this combination are warranted. |