| General information |
| Database: | DB00165 |
| Objective: | Programmed death 1 (PD1) protein, a Tcell coinhibitory receptor, and one of its ligands, PDL1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD1 and PDL1 enhances immune function in vitro and mediates antitumor activity in preclinical models. |
| Authors: | Brahmer JR, et al |
| Title: | Safety and activity of antiPDL1 antibody in patients with advanced cancer. |
| Journal: | N Engl J Med. |
| Year: | 2012 |
| PMID: | 22658128 |
| Trial Design |
| Clinical Trial Id: | NCT00729664. |
| Agent: | BMS936559
|
| Target: | Programmed cell death ligand 1 (PDL1)
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multicenterphase I trial |
| Key Patients Feature: | Patients were required to have documented advanced non-smallcell lung cancer, melanoma, renalcell cancer, ovarian cancer, colorectal cancer, pancreatic cancer, gastric cancer, or breast cancer and have had tumor progression after at least one previous course of tumorappropriate therapy for advanced or metastatic disease |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | they administered intravenous antiPDL1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. AntiPDL1 antibody was administered every 14 days in 6week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. |
| Primary End Point: | the safety and adverseevent profiles of anti-PDL1 antibody. |
| Secondary End Point: | the antitumor activity of the antibody and its pharmacokinetics. Pharmacodynamic measures were included as exploratory objectives. |
| Patients Number: | 207 |
| Trial Results |
| DLT_MTD: | A maximum tolerated dose was not reached. |
| Objective Response Rate: | Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renalcell cancer, 5 of 49 with non small cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of followup. |
| 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): | Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. |
| Conclusions: | Antibodymediated blockade of PDL1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non small cell lung cancer, melanoma, and renalcell cancer. |