First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: Safety, efficacy, and correlation of outcomes with PD-L1 status.

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 8024)
Scott N. Gettinger, Frances A. Shepherd, Scott Joseph Antonia, Julie R. Brahmer, Laura Quan Man Chow, Rosalyn A. Juergens, Hossein Borghaei, Yun Shen, Christopher Harbison, Suresh Alaparthy, Allen C. Chen, Naiyer A. Rizvi; Yale Cancer Center, New Haven, CT; Princess Margaret Cancer Centre, Toronto, ON, Canada; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; University of Washington, Seattle, WA; Juravinski Cancer Centre, Hamilton, ON, Canada; Fox Chase Cancer Center, Philadelphia, PA; Bristol-Myers Squibb, Princeton, NJ; Memorial Sloan-Kettering Cancer Center, New York, NY

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Abstract Disclosures


Background: The fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody nivolumab has demonstrated durable responses and tolerability in patients (pts) with previously treated advanced NSCLC. Tumor PD-1 ligand (PD-L1) expression is being studied as a potential biomarker for nivolumab. We report interim phase I results of first-line nivolumab in chemotherapy-naïve advanced NSCLC pts. Methods: Pts with squamous (sq) or non-sq advanced NSCLC received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity (post-progression treatment allowed based on protocol-defined criteria). Responses (RECIST 1.1) were evaluated overall and according to tumor PD-L1 status (PD-L1+ = ≥5% tumor cells expressing PD-L1 [Dako immunohistochemistry assay]). Results on the first 20 pts are included. Results: After ≥6 months follow up, 17 pts (85%) experienced any-grade treatment-related adverse events (AEs), managed with standard algorithms. Treatment-related grade 3-4 AEs (3 pts, 15%) were AST or ALT elevations, hyperglycemia, and rash (n=1 each). No pneumonitis (any grade) was observed. Objective response rate (ORR) was 30% (Table); 5/6 responders (83%) achieved response by first scan (wk 11). Two pts had >80% target lesion reduction at 18 wks. Of 15 evaluable tumor samples, 9 were PD-L1+. ORR was 67% in PD-L1+ pts; no responses were observed in the 6 PD-L1- pts. Responses were durable (median duration of response [mDOR] not reached [NR]; 5 ongoing responses). Conclusions: In this phase I study, nivolumab led to early, durable responses in advanced NSCLC pts, with a tolerable safety profile. PD-L1 status appeared to correlate with ORR/progression-free survival (PFS). Follow up and responses of 30 additional treated pts will be reported. These data support further studies of first-line nivolumab monotherapy in advanced NSCLC. Clinical trial information: NCT01454102.

ORR   mDOR Median PFS
n/N (%)   wk (range)
All pts 6/20 (30) NR (11.1+, 37.7+) 29.6 (5.9, 47.6+)
Non-sq 4/11 (36) NR (36.1, 37.7+) 45.6 (9.6, 47.6+)
Sq 2/9 (22) NR (11.1+, 27.9+) 15.1 (5.9, 37.9+)
PD-L1+ 6/9 (67) NR (11.1+, 37.7+) NR (8, 47.6+)
PD-L1- 0/6 n/a 23.1 (9.6, 47.3+)
PD-L1 unknown 0/5 n/a 15.1 (5.9, 35.7+)