Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial.

Developmental Therapeutics - Immunotherapy
Session Type and Session Title: 
Oral Abstract Session, Developmental Therapeutics - Immunotherapy
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 3002^)
Suzanne Louise Topalian, Mario Sznol, Julie R. Brahmer, David F. McDermott, David C. Smith, Scott N. Gettinger, Janis M. Taube, Charles G. Drake, Drew M. Pardoll, John D. Powderly, Richard D. Carvajal, Jeffrey Alan Sosman, Michael B. Atkins, Scott J. Antonia, David R. Spigel, Donald P. Lawrence, Georgia Kollia, Ashok Kumar Gupta, Jon M. Wigginton, F. Stephen Hodi; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Yale Cancer Center, New Haven, CT; Beth Israel Deaconess Medical Center, Boston, MA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Yale University, New Haven, CT; Johns Hopkins School of Medicine, Baltimore, MD; Carolina BioOncology Institute, Huntersville, NC; Memorial Sloan-Kettering Cancer Center, New York, NY; Vanderbilt University Medical Center, Nashville, TN; Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN; Massachusetts General Hospital Cancer Center, Boston, MA; Bristol-Myers Squibb, Princeton, NJ; Dana-Farber Cancer Institute, Boston, MA

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

Abstract Disclosures


Background: Blockade of programmed death-1 (PD-1), a co-inhibitory receptor expressed by activated T cells, can overcome immune resistance and mediate tumor regression (Topalian et al., NEJM 2012). Here we present long-term safety and efficacy outcomes from a phase I study of nivolumab, a PD-1 blocking mAb, in patients (pts) with advanced solid tumors. Methods: Pts enrolled between 2008-2012 received nivolumab (0.1−10 mg/kg IV Q2W) during dose escalation and/or cohort expansion. Tumors were assessed by RECIST 1.0 after each 4-dose cycle. Pts received ≤12 cycles until unacceptable toxicity, confirmed progression, or CR. Results: 304 pts with non-small cell lung cancer (NSCLC, n=127, squamous and nonsquamous), melanoma (MEL, n=107), renal cell (RCC, n=34), colorectal (n=19) or prostate cancer (n=17) were treated. Durable ORs (CR/PR) were observed in MEL, NSCLC and RCC (Table); in 54 responders with ≥1 yr follow-up, 28 lasted ≥1 yr. Median OS in these heavily pretreated pts (47% with 3-5 prior systemic therapies) compared favorably with expected outcomes as of July 2012. Drug-related AEs (any grade) occurred in 72% (220/304) and G3/G4 AEs in 15% (45/304) of pts. Drug-related pneumonitis occurred in 3% (10/304), including G3/G4 in 1% (3/304), resulting in 3 deaths early in the trial, which led to increased clinical monitoring and an emphasis on management algorithms. Nivolumab-related pneumonitis characteristics and management will be summarized. Updated survival and safety data from Feb 2013 (≥1 yr follow-up all pts) will be presented, including OS at 3 yr. Conclusions: Nivolumab produced sustained survival with a manageable long-term safety profile in advanced MEL, NSCLC and RCC, supporting its ongoing clinical development in controlled phase III trials with survival endpoints. Clinical trial information: NCT00730639.

No. pts (%)
OS median,
(95% CI)
OS rate, %a
(95% CI); pts at risk, n
1 Yr 2 Yr
MEL 0.1−10 33/106 (31) 16.8
(12.5 – NR)
(52-71); 50
(33-56); 24
NSCLC 1−10 20/122 (16) 9.6
(33-53); 24
(18-47); 4
RCC 1 or 10 10/34 (29) >22 70
(55-86); 22
(32-72); 7

aOS estimates after 1 yr reflect censoring and shorter follow-up for pts enrolling later in the study. NR = Not reached.