104PD - Phase 2 study of nivolumab (anti-programmed death-1 [PD-1]) in patients (pts) with advanced, refractory squamous (SQ) non-small cell lung cancer (NS...

Date 16 April 2015
Event ELCC 2015
Session Advanced NSCLC
Topics Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Gerard Zalcman
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors G. Zalcman1, N.A. Rizvi2, H. Lena3, J. Wolf4, J. Mazieres5, S.J. Antonia6, E. Minenza7, D. Planchard8, B.J. Lestini9, S.S. Ramalingam10
  • 1Pneumonology, CHU de Caen, 14033 - Caen/FR
  • 2Thoracic Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 3Oncology And Pulmonology, Centre Hospitalier Universitaire de Rennes, Rennes/FR
  • 4Pulmonary Oncology, Universitaetsklinik Koeln, Koeln/DE
  • 5Thoracic Oncology, Hôpital Larrey, Centre Hospitalier Universitaire de Toulouse, Toulouse/FR
  • 6Thoracic Oncology, H. Lee Moffitt Cancer Center, Tampa/US
  • 7Oncology, Ospedale S. Maria, Terni/IT
  • 8Thoracic Oncology, Gustave Roussy, Villejuif/FR
  • 9Oncology Global Clinical Research, Bristol-Myers Squibb, Princeton/US
  • 10Department Of Hematology & Medical Oncology, Winship Cancer Institute, Emory University, Atlanta/US



Pts with SQ NSCLC refractory to multiple prior treatment regimens have poor outcomes. We report results from a phase 2, single-arm study of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, in pts with advanced, refractory, SQ NSCLC (NCT01721759).


Pts (≥2 prior therapies) (N = 117) received nivolumab 3 mg/kg every 2 wks until progression or unacceptable toxicity. Primary endpoint was confirmed objective response rate (ORR), assessed by an independent radiology review committee (IRC) per RECIST v1.1. Secondary and exploratory objectives included investigator-assessed ORR, progression-free survival (PFS), overall survival (OS), safety, and ORR by pt subgroups and by PD-L1 status (PD-L1+ defined as ≥5% of tumor cells with cell surface staining).


IRC-assessed ORR was 15% (17/117) with a minimum of 11 mos follow-up. Median time to response was 3 mos (range, 2–9) with median duration of response not reached (range, 2+ to 12+ mos) and 76% (13/17) of responses ongoing. An additional 26% of pts had stable disease with median duration of 6 mos. One-year PFS rate was 20% (95% CI: 13, 29) and median PFS was 2 mos (95% CI: 2, 3). One-year OS rate was 41% (95% CI: 32, 50) and median OS was 8 mos (95% CI: 6, 11). Objective responses were observed across subgroups including age and prior therapies (Table). ORRs for pts with PD-L1+ and PD-L1 tumors were 24% (6/25) and 14% (7/51), respectively. Grade 3–4 treatment-related adverse events (AEs) were reported in 17% of pts, including: fatigue (4%), pneumonitis (3%), and diarrhea (3%). AEs were manageable with established safety guidelines. Two treatment-associated deaths (pneumonia; ischemic stroke) occurred in pts with multiple comorbidities in the setting of progressive disease.

Characteristic All treated pts (N = 117) % (n) ORR % (n/N) [95% CI]
Age, yrs
<65 ≥65 and <75 ≥75 50 (58) 37 (43) 14 (16) 12 (7/58) [5–23] 21 (9/43) [10–36] 6 (1/16) [0.2–30]
Number of prior systemic therapies
2 3 ≥4 35 (41) 44 (52) 21 (24) 10 (4/41) [3–23] 17 (9/52) [8–30] 17 (4/24) [5–37]
Characteristic All treated pts (N = 117) % (n)
Former or current smoker 92 (108)
Best response to most recent prior therapy
Complete or partial response Stable disease Progressive disease Unknown 4 (5) 27 (32) 61 (71) 8 (9)
Time from most recent prior regimen to treatment, mos
<3 mos 3–6 mos >6 mos 76 (89) 14 (16) 10 (12)


Nivolumab demonstrated clinically meaningful efficacy and a manageable safety profile in pts with advanced, refractory, SQ NSCLC.

Clinical trial identification NCT01721759


All authors report non-financial support from StemScientific, during the conduct of the study. Additionally:

G. Zalcman: personal fees from Bristol Myers Squibb, outside the submitted work.

N.A. Rizvi: personal fees from Bristol-Myers Squibb, Genentech/Roche, MedImmune/AstraZeneca, and Merck, outside the submitted work.

H. Lena: personal fees and non-financial support from Bristol-Myers Squibb, personal fees from Merck, non-financial support from Roche, outside the submitted work.

J. Wolf: personal fees-Bristol-Myers Squibb, AstraZeneca, Clovis & Merck (MSD); grants & personal fees-Boehringer-Ingelheim, Novartis, Pfizer & Roche; grants-Bayer outside submitted work.

S.J. Antonia: grants and personal fees from MedImmune, personal fees from Bristol Myers Squibb, personal fees from AstraZeneca, outside the submitted work.

D. Planchard: advisory board fees from Merck, Roche, AstraZeneca, BI, Lilly, Pfizer

B.J. Lestini: employee/owns stock - Bristol Myers Squibb.

S.S. Ramalingam: grants & personal fees: Bristol-Myers Squibb; personal fees: Amgen, AZ, Aveo, BI, Celgene, Genentech, Lilly & Novartis, outside submitted work.

All other authors have declared no conflicts of interest.