| General information |
| Database: | DB00164 |
| Objective: | Blockade of programmed death 1 (PD1), an inhibitory receptor expressed by T cells, can overcome immune resistance. They assessed the antitumor activity and safety of BMS936558, an antibody that specifically blocks PD1. |
| Authors: | Topalian SL, et al |
| Title: | Safety, activity, and immune correlates of antiPD1 antibody in cancer. |
| Journal: | N Engl J Med. |
| Year: | 2012 |
| PMID: | 22658127 |
| Trial Design |
| Clinical Trial Id: | NCT00730639. |
| Agent: | BMS936558
|
| 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: | multipledosephase I trial |
| Key Patients Feature: | patients with advanced melanoma, non small cell lung cancer, castrationresistant prostate cancer, or renalcell or colorectal cancer |
| Biomarker: | intratumoral PD1 ligand (PDL1) expression in the modulation of the PD1PDL1 pathway |
| Biomark Analysis: | immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PDL1negative tumors, none had an objective response; 9 of 25 patients (36%) with PDL1positive tumors had an objective response (P=0.006). |
| Control Group Info: | single arm |
| Treatment Info: | pts to receive antiPD1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. |
| Primary End Point: | safety, antitumor activity, and pharmacokinetics |
| Secondary End Point: | NA |
| Patients Number: | 296 |
| Trial Results |
| DLT_MTD: | No maximum tolerated dose was defined. |
| Objective Response Rate: | objective responses (complete or partial responses) were observed in those with non small cell lung cancer, melanoma, or renalcell cancer. Cumulative response rates (all doses) were 18% among patients with non small cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renalcell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more 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 drugrelated adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. Adverse events consistent with immunerelated causes were observed. |
| Conclusions: | AntiPD1 antibody produced objective responses in approximately one in four to one in five patients with non small cell lung cancer, melanoma, or renalcell cancer; the adverseevent profile does not appear to preclude its use. Preliminary data suggest a relationship bettheyen PDL1 expression on tumor cells and objective response. |