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Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial.
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Background: We have shown that nivolumab, a fully human IgG4 PD-1 immune-checkpoint inhibitor antibody, is tolerable and active in pts with advanced solid tumors in a large phase I trial (Topalian et al. N Eng J Med 366:2443-54, 2012). For the MEL pts in this trial, we report long-term clinical activity, pts’ response off therapy, tumor PD-1 ligand (PD-L1) expression associated with survival endpoints, and for the first time, 3-y overall survival (OS). Methods: Previously treated advanced MEL pts with no prior ipilimumab therapy received nivolumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) Q2Wk for ≤96 wk and were evaluated for OS and progression-free survival (PFS). PD-L1 tumor cell membrane expression was retrospectively assessed in archival specimens by a Dako immunohistochemistry assay with ≥5% tumor cells designated as PD-L1(+). Results: From 2008-2012, 107 MEL pts initiated treatment with nivolumab; 25% had ≥3 prior therapies. Across doses, the 2- and 3-y OS rates were 48 and 41%, respectively (Table). For the 34/107 (32%) pts with objective responses (OR; RECIST), median response duration was 22.9 mo. Twenty-four OR pts stopped nivolumab for reasons other than disease progression; 11 (46%) maintained responses for ≥24 wk off drug (range: 24, 56+ wk). Four (4%) pts had unconventional “immune-related” responses. In a subset of pts with evaluable tumor samples (41/107), pts with PD-L1(+) and (–) tumors (n=18 and 23, respectively) had median OS of not reached and 12.5 mo; median PFS was 9.1 mo and 1.9 mo. Safety has been previously reported (Sznol et al. J Clin Oncol 31:abs CRA9006, 2013). Conclusions: In advanced MEL pts, nivolumab demonstrated favorable 2- and 3-y OS rates, durable responses with a number persisting off therapy, and an acceptable safety profile. Additional analyses will be presented by pts’ characteristics across the full population, the long-term survival subgroup, and the PD-L1(+/–) tumor subgroups. Ongoing phase III trials are further evaluating nivolumab for MEL pts and PD-L1 as a potential predictive biomarker for response to nivolumab. Clinical trial information: NCT00730639.
|n=107||% (95% CI)||Pts at risk|
||63 (53, 71)||63|
||48 (38, 57)||44|
||41 (31, 51)||22|
*September 2013 analysis.
Abstracts by F. Stephen Hodi:
T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade.Meeting: 2016 Genitourinary Cancers Symposium | Abstract No: 501Category: Genitourinary Cancer - Renal Cell Cancer
A multi-center phase II open-label study (CheckMate 204) to evaluate safety and efficacy of nivolumab (NIVO) in combination with ipilimumab (IPI) followed by NIVO monotherapy in patients (pts) with melanoma (MEL) metastatic to the brain.Meeting: 2015 ASCO Annual Meeting | Abstract No: TPS9080
A multicenter, open-label trial of talimogene laherparepvec (T-VEC) plus pembrolizumab vs pembrolizumab monotherapy in previously untreated, unresected, stage IIIB-IV melanoma.Meeting: 2015 ASCO Annual Meeting | Abstract No: TPS9081
Presentations by F. Stephen Hodi:
Clinical activity and safety of anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced melanoma (MEL).Meeting: 2012 ASCO Annual Meeting Abstract No: 8507Session: Melanoma/Skin Cancers (Oral Abstract Session)
Immune-Related Response Criteria: Description and Use in the Management of CTLA-4 Blocking Antibody-Treated PatientsMeeting: 2012 ASCO Annual MeetingSession: Immunotherapy with the T-Cell Checkpoint Antibodies: Implications for the Practitioner (Education Session)
A phase I trial of ipilimumab plus bevacizumab in patients with unresectable stage III or stage IV melanoma.Meeting: 2011 ASCO Annual Meeting Abstract No: 8511Session: Melanoma/Skin Cancers (Oral Abstract Session)