Clinical activity and safety of anti-PD1 (BMS-936558, MDX-1106) in patients with advanced non-small-cell lung cancer (NSCLC).

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Clinical Science Symposium, Emerging New Targets and New Drugs in Non-small Cell Lung Cancer
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr 7509)
Julie R. Brahmer, Leora Horn, Scott Antonia, David R. Spigel, Leena Gandhi, Lecia V. Sequist, Jon Wigginton, Dan McDonald, Georgia Kollia, Ashok Kumar Gupta, Scott N. Gettinger; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Vanderbilt-Ingram Cancer Center, Nashville, TN; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; SCRI/Tennessee Oncology, PLLC, Nashville, TN; Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA; Bristol-Myers Squibb, Princeton, NJ; Yale University School of Medicine, New Haven, CT

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: BMS-936558 is a fully human mAb that blocks the programmed death-1 (PD-1) co-inhibitory receptor expressed by activated T cells. We report here that BMS-936558 mediates antitumor activity in heavily pretreated patients (pts) with advanced NSCLC, a tumor historically not considered to be responsive to immunotherapy. Methods: BMS-936558 was administered IV Q2WK to pts with various solid tumors, including NSCLC, at doses of 0.1 to 10 mg/kg during dose-escalation and/or cohort expansion. Pts with advanced NSCLC previously treated with at least 1 prior chemotherapy regimen were eligible. Pts received up to 12 cycles (4 doses/cycle) of treatment or until PD or CR. Clinical activity was assessed by RECIST 1.0. Results: Of 240 pts treated as of July 1, 2011, 75 NSCLC pts were treated at 1 (n=17), 3 (n= 19), or 10 mg/kg (n=39). ECOG performance status was 0/1/2 in 24/49/2 pts. Tumor histology was squamous (n=17), non-squamous (n=52), or unknown (n=6). The number of prior therapies was 1 (n=9), 2 (n=20), ≥3 (n=45), or unknown (n=1). Ninety-five percent of pts had received platinum-based chemotherapy and 40% had a prior tyrosine kinase inhibitor. Sites of metastatic disease included lymph node (n=50), liver (n=12), lung (n=62), and bone (n=13). Median duration of therapy was 10 wk (max 100 wk). Common related AEs were fatigue (17%), nausea (11%), pyrexia (7%), pruritus (7%), dizziness (7%), and anemia (7%). The incidence of grade 3-4 related AEs was 8%. There was 1 drug-related death due to pulmonary toxicity. Clinical activity was observed at all dose levels (Table) and in multiple histologies. Several pts had prolonged SD. Some had a persistent decrease in overall tumor burden in the presence of new lesions and were not categorized as responders. At the time of data lock, of 10 OR pts, 3 had responses lasting ≥6 mo and 5 were on study with response duration of 1.8-5.5 mo. Conclusions: BMS-936558 is well tolerated and has encouraging clinical activity in pts with previously treated advanced NSCLC. Further development of BMS-936558 in pts with advanced NSCLC is warranted.
Dose (mg/kg) na ORb uPRc RRd (%)
1 18 1 - 6
3 18 3 2 28
10 37 6 1 19

aResponse evaluable pts.

bCR or PR.

cUnconfirmed PR.

dResponse rate [(OR + uPR) ÷ n].