Nivolumab (anti-PD-1; BMS-936558, ONO-4538) and ipilimumab in first-line NSCLC: Interim phase I results.

Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Poster Highlights Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 8023)
Scott Joseph Antonia, Scott N. Gettinger, Laura Quan Man Chow, Rosalyn A. Juergens, Hossein Borghaei, Yun Shen, Christopher Harbison, Allen C. Chen, Neal Ready, Naiyer A. Rizvi; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; Yale Cancer Center, New Haven, CT; University of Washington, Seattle, WA; Juravinski Cancer Centre, Hamilton, ON, Canada; Fox Chase Cancer Center, Philadelphia, PA; Bristol-Myers Squibb, Princeton, NJ; Duke University Medical Center, Durham, NC; Memorial Sloan-Kettering Cancer Center, New York, NY

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

Abstract Disclosures


Background: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, and ipilimumab, an IgG1 CTLA-4 checkpoint receptor blocking antibody, have shown activity in advanced NSCLC; clinical data in melanoma showed improved responses and a manageable safety profile when combined. We report interim results from a phase I study evaluating first-line nivolumab + ipilimumab (N+I) in advanced NSCLC patients (pts). Methods: Chemotherapy-naive pts (n=46) with squamous (sq) or non-sq NSCLC received the 3 + 1 mg/kg or 1 + 3 mg/kg combination dose IV Q3W for 4 cycles followed by nivolumab 3 mg/kg IV Q2W until progression/unacceptable toxicity. Objective response rate (ORR; RECIST 1.1) was evaluated overall and by baseline tumor PD-L1 status (Dako immunohistochemistry assay). After an amendment, a 1 + 1 mg/kg cohort was added (n=30, data immature at Dec 2013 analysis). Results: In the 4 cohorts with ≥4 months follow up, any-grade treatment-related adverse events (managed with protocol algorithms) were reported in 39 pts (85%; grade 3–4 in 22 pts [48%]) and led to discontinuation in 16 pts. Treatment-related deaths (n=3) were due to respiratory failure, bronchopulmonary hemorrhage and toxic epidermal necrolysis. Responses occurred in all 4 cohorts (Table); overall ORRb was 22% (median duration of response [mDOR] not reached [NR]) and stable disease (SD) 33% (range 13 – 34.1+ wks); 2 pts exhibited unconventional “immune related” responses. In 29 evaluable tumor samples from the study, ORR did not correlate with PD-L1 status. Conclusions: These interim data in pts with advanced NSCLC suggest that a nivolumab + ipilimumab immunotherapy regimen is feasible and demonstrates antitumor activity in both PD-L1+ and PD-L1– pts. Safety will be further assessed at the 1 + 1 mg/kg dose. The recommended combination dose for phase II/III evaluation has not been determined. Clinical trial information: NCT01454102.

N1 + I3
N1 + I3
N3 + I1
N3 + I1
N 7 15 8 16
ORR,a n (%) 1 (14) 1 (7) 2 (25) 2 (13)
ORR,b n (%) 1 (14) 2 (13) 3 (38) 4 (25)
3 (14) 7 (29)
SD, n (%) 2 (29) 6 (40) 4 (50) 3 (19)
mDOR (Kaplan-Meier),a
wk (range)
NR (9+) NR (21+) 17 (12, 21) NR (24+, 25+)
Ongoing responders,a
n (%)
1 (100) 1 (100) 0 2 (100)

a Confirmed OR only. b Confirmed + unconfirmed OR.