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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 phase 1/3 multicenter trial of talimogene laherparepvec in combination with pembrolizumab for unresected, stage IIIB-IV melanoma (MASTERKEY-265).Meeting: 2016 ASCO Annual Meeting | Abstract No: TPS9598Category: Melanoma/Skin Cancers - Advanced Disease
Meeting: 2016 ASCO Annual Meeting
| Abstract No: 11506
Category: Tumor Biology - Immunobiology
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)