| General information |
| Database: | DB00502 |
| Objective: | Programmed death1 (PD1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. Thisphase I study sought to determine the safety and tolerability of antiPD1 blockade in patients with treatmentrefractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. |
| Authors: | Brahmer JR, et al |
| Title: | Phase I study of singleagent antiprogrammed death1 (MDX1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20516446 |
| Trial Design |
| Clinical Trial Id: | NCT00441337 |
| Agent: | MDX1106
|
| Target: | PD1
|
| 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: | Eligible patients had treatmentrefractory metastatic melanoma, castrateresistant prostate cancer, renal cell carcinoma (RCC), non-smallcelllung cancer (non small cell lung cancer), or colorectal cancer (CRC), and had no cancer therapyfor at least 4 weeks before enrollment. Patients were 18 years old with a lifeexpectancy of 12 weeks, an Eastern Cooperative Oncology Group (ECOG)performance status of 0 or 1, adequate organ function, and no ongoing systemic infections or history of autoimmune disease. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received a single intravenous infusion of antiPD1 (MDX1106) in doseescalating sixpatient cohorts at 0.3, 1, 3, or 10 mg/kg, follotheyd by a 15patient expansion cohort at 10 mg/kg. |
| Primary End Point: | the safety and tolerability of a single dose of MDX1106 to determine the maximumtolerated dose (MTD) and pharmacokinetics. |
| Secondary End Point: | assessing antitumor activity, pharmacodynamics, and immunologic end points. |
| Patients Number: | 39 |
| Trial Results |
| DLT_MTD: | no DLTs were observed after onedose, and an MTD was not defined in this study. Grade 2 adverseclinical and laboratory events are summarized in Appendix |
| Objective Response Rate: | One durable complete response(CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients(melanoma, non small cell lung cancer) had significant lesional tumor regressions not meeting PR criteri |
| 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): | MDX1106 was welltolerated: no DLTs were observed after one dose, and an MTD was not defined in this study. Most frequent were decreased CD4 lymphocytecounts (14 patients, 35.9%), lymphopenia (10 patients, 25.6%), fatigue and musculoskeletal events (six patients each, 15.4%). No patient developed human antihuman Ab, even after multiple doses. |
| Conclusions: | Blocking the PD1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, andor other checkpoint inhibitors is warranted. |