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Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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 rate, %a
(95% CI); pts at risk, n
|1 Yr||2 Yr|
(12.5 – NR)
|RCC||1 or 10||10/34 (29)||>22||70
aOS estimates after 1 yr reflect censoring and shorter follow-up for pts enrolling later in the study. NR = Not reached.
Abstracts by S. L. Topalian:
Safety and antitumor activity of biweekly MDX-1106 (Anti-PD-1, BMS-936558/ONO-4538) in patients with advanced refractory malignancies.Meeting: 2010 ASCO Annual Meeting | Abstract No: 2506
Phase II experience with MDX-1106 (Ono-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies.Meeting: 2009 ASCO Annual Meeting | Abstract No: 3018