| General information |
| Database: | DB00839 |
| Objective: | a phase I study assessed the safety, tolerability, pharmacokinetics, and preliminary antitumor effect of mapatumumab, a fullyhuman agonist monoclonal antibody to the tumor necrosis factorrelated apoptosisinducing ligand receptor 1 (TRAILR1, DR4), in combination with paclitaxel and carboplatin. |
| Authors: | Leong S, et al |
| Title: | Mapatumumab, an antibody targeting TRAILR1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19652058 |
| 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 + paclitaxel + carboplatin |
| Study Type: | a phase I and pharmacokinetic study |
| Key Patients Feature: | Patients with histologically or cytologically documented solid malignancies refractory to standard therapy, for which no standard exists, or for which the combination of paclitaxel and carboplatin was considered an appropriate standard treatment were eligible. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received 3, 10, or 20 mg/kg of mapatumumab with standard doses of paclitaxel and carboplatin every 21 days for up to six cycles in the absence of disease progression. Additional cycles of paclitaxel and/or mapatumumab were permissible in selected cases. |
| Primary End Point: | the safety and tolerability of escalating doses of mapatumumab with paclitaxel and carboplatin, to explore evidence of pharmacokinetic interactions and mapatumumab immunogenicity, and to evaluate preliminary antitumor activity of the combination |
| Secondary End Point: | NA |
| Patients Number: | 27 |
| Trial Results |
| DLT_MTD: | The maximumtolerated dose (MTD) was defined as the highest dose at which less than two of six patients experienced a hematologic or nonhematologic treatmentrelated doselimiting toxicity (DLT). DLT was defined as the following adverse events (AEs) considered possibly, probably, or definitely related to any of the study drugs (mapatumumab, paclitaxel, and/or carboplatin) occurring during the first 21 days of treatment: grade 4 neutropenia lasting for more than 7 consecutive days, febrile neutropenia, or grade 4 thrombocytopenia, or grade more than and equal to 3 nonhematologic AEs. Nausea/vomiting, neuropathy, and fatigue were only considered |
| Objective Response Rate: | 63% |
| 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 toxicities included alopecia, neutropenia, fatigue, and anemia. Neutropenia occurred during approximately 35% of courses in the 10 and 20 mg/kg cohorts. Grade 3 and 4 lymphopenias were observed in 37% and 22% of the patients, respectively, although the subpopulation of affected lymphocytes was not analyzed. |
| Conclusions: | Mapatumumab is welltolerated up to 20 mgkg in combination with paclitaxel and carboplatin. There are no apparent pharmacokinetic interactions among the drugs. Preliminary anticancer activity demonstrated clinical benefit for the majority of these patients |