| General information |
| Database: | DB00163 |
| 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: | a phase I clinical trial |
| Key Patients Feature: | patients with advanced metastatic melanoma, colorectal cancer (CRC), castrateresistant prostate cancer, non small cell lung cancer (non small cell lung cancer), or renal cell carcinoma (RCC) |
| Biomarker: | tumor cell surface B7H1 expression |
| Biomark Analysis: | Exploratory analyses revealed baseline levels of cytokeratin 19 fragment antigen 211, neuronspecific enolase, proGRP, and circulating tumor cell number as correlates of clinical benefit. |
| Control Group Info: | single arm |
| Treatment Info: | 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. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. |
| Primary End Point: | the safety, antitumor activity, pharmacodynamics, and correlative in vitro results |
| Secondary End Point: | NA |
| Patients Number: | 39 |
| Trial Results |
| DLT_MTD: | AntiPD1 was well tolerated:no DLTs were observed after one dose, and an MTD was not defined in this study. |
| 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 criteria. |
| 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): | Most frequent were decreased CD4+ lymphocyte counts (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. one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. |
| 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. |