Étude de phase III, CheckMate 017 comparant en seconde ligne nivolumab et docétaxel dans les cancers épidermoïdes (1) Nivolumab 3 mg/kg toutes les 2 semaines jusqu’à progression ou toxicité n = 135 272 cancers épidermoides PS 0-1 Prétraité (une seule ligne à base de platine) Biopsie archivée disponible R 1:1 Docétaxel 75 mg/m2 toutes les 3 sem. 6 cycles jusqu’à progression ou toxicité n = 137 Objectif principal : SG Objectifs secondaires RO RECIST 1.1 SSP QDV Tolérance Efficacité selon l’expression du PD-L1 8009 - A phase III study (CheckMate 017) of nivolumab (NIVO; anti-programmed death-1 [PD-1]) vs docetaxel (DOC) in previously treated advanced or metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC).   Session: Immunotherapy in Lung Cancer: A Paradigm Shift Type: Clinical Science Symposium Time: Sunday May 31, 4:30 PM to 6:00 PM Location: E Hall D1 Citation:Abstract: Background: Treatment options are limited for patients (pts) with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC). We report results of a randomized, open-label, global phase III study of NIVO, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, vs DOC in pts with SQ NSCLC and with disease progression (PD) during/after one prior PT-DC regimen. Methods: Pts (N = 272) were randomized 1:1 to receive NIVO 3 mg/kg (n = 135) Q2W or DOC 75 mg/m2(n = 137) Q3W until PD, discontinuation due to toxicity, or other reasons. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), quality of life, and safety. Results:Superior OS was observed with NIVO vs DOC (HR = 0.59; 95% CI: 0.44, 0.79; p = 0.00025). NIVO improved PFS vs DOC (HR = 0.62; 95% CI: 0.47, 0.81; p = 0.0004). ORR was 20% (27/135) for NIVO and 9% (12/137) for DOC (p = 0.0083). OS HRs favored NIVO regardless of PD-L1 expression (Table). Grade 3–4 drug-related AEs occurred in 7% (9/131) of NIVO and 55% (71/129) of DOC pts. No deaths were related to NIVO vs 3 DOC-related deaths. Conclusions: CheckMate 017 met its primary objective, demonstrating superior OS of NIVO vs DOC in pts with advanced, previously treated SQ NSCLC and demonstrated PFS and ORR superiority. Tumor PD-L1 status was neither prognostic nor predictive for efficacy endpoints. The safety profile of NIVO 3 mg/kg Q2W is acceptable and favorable vs DOC. NIVO represents a significant improvement in second-line therapy for SQ NSCLC. Clinical trial information: NCT01642004 NIVO (n = 135) DOC (n = 137) mOS, mo (95% CI) 9.2 (7.3, 13.3) 6.0 (5.1, 7.3) 1-yr OS, % (95% CI) 42 (34, 50) 24 (17, 31) Median duration of response, mo (range) Not Reached (2.9–20.5+) 8.4 (1.4+–15.2+) mPFS, mo (95% CI) 3.5 (2.1, 4.9) 2.8 (2.1, 3.5) 1-yr PFS, % (95% CI) 21 (14, 28) 6 (3, 12) PD-1 expression NIVO (n) DOC (n) OS HR (95% CI) ≥ 1% 63 56 0.69 (0.45, 1.05) < 1% 54 52 0.58 (0.37, 0.92) ≥ 5% 42 39 0.53 (0.31, 0.89) < 5% 75 69 0.70 (0.47, 1.02) ≥ 10% 36 33 0.50 (0.28, 0.89) < 10% 81 0.70 (0.48, 1.01) ASCO® 2015 - D’après Spiegel D et al., abstr. 8009, actualisé

Étude de phase III, CheckMate 017 comparant en seconde ligne nivolumab et docétaxel dans les cancers épidermoïdes (2) Nivolumab (n = 135) Docétaxel (n = 137) Âge médian (ans) 62 64 Homme (%) 82 71 ECOG PS 0/1 (%) 21/78 18/82 Métastases cérébrales (%) 7 6 Paclitaxel antérieur (%) 34 ASCO® 2015 - D’après Spiegel D et al., abstr. 8009, actualisé

Étude de phase III, CheckMate 017 comparant en seconde ligne nivolumab et docétaxel dans les cancers épidermoïdes (3)   Nivolumab (n = 135) Docétaxel (n = 137) RO % 20 9 SG médiane, % (IC95) 9,2 (7,3-13,3) 6,0 (5,1-7,3) SG à 1 an, % (IC95) 42 (34-50) 24 (17-31) Durée médiane de réponse (mois) Non atteinte (2,9–20,5+) 8,4 (1,4+–15,2+) SSP médiane, % (IC95) 3,5 (2,1- 4,9) 2,8 (2,1-3,5) SSP à 1 an, % (IC95) 21 (14-28) 6 (3-12) 8009 - A phase III study (CheckMate 017) of nivolumab (NIVO; anti-programmed death-1 [PD-1]) vs docetaxel (DOC) in previously treated advanced or metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC).   Session: Immunotherapy in Lung Cancer: A Paradigm Shift Type: Clinical Science Symposium Time: Sunday May 31, 4:30 PM to 6:00 PM Location: E Hall D1 Citation:Abstract: Background: Treatment options are limited for patients (pts) with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC). We report results of a randomized, open-label, global phase III study of NIVO, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, vs DOC in pts with SQ NSCLC and with disease progression (PD) during/after one prior PT-DC regimen. Methods: Pts (N = 272) were randomized 1:1 to receive NIVO 3 mg/kg (n = 135) Q2W or DOC 75 mg/m2(n = 137) Q3W until PD, discontinuation due to toxicity, or other reasons. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), quality of life, and safety. Results:Superior OS was observed with NIVO vs DOC (HR = 0.59; 95% CI: 0.44, 0.79; p = 0.00025). NIVO improved PFS vs DOC (HR = 0.62; 95% CI: 0.47, 0.81; p = 0.0004). ORR was 20% (27/135) for NIVO and 9% (12/137) for DOC (p = 0.0083). OS HRs favored NIVO regardless of PD-L1 expression (Table). Grade 3–4 drug-related AEs occurred in 7% (9/131) of NIVO and 55% (71/129) of DOC pts. No deaths were related to NIVO vs 3 DOC-related deaths. Conclusions: CheckMate 017 met its primary objective, demonstrating superior OS of NIVO vs DOC in pts with advanced, previously treated SQ NSCLC and demonstrated PFS and ORR superiority. Tumor PD-L1 status was neither prognostic nor predictive for efficacy endpoints. The safety profile of NIVO 3 mg/kg Q2W is acceptable and favorable vs DOC. NIVO represents a significant improvement in second-line therapy for SQ NSCLC. Clinical trial information: NCT01642004 NIVO (n = 135) DOC (n = 137) mOS, mo (95% CI) 9.2 (7.3, 13.3) 6.0 (5.1, 7.3) 1-yr OS, % (95% CI) 42 (34, 50) 24 (17, 31) Median duration of response, mo (range) Not Reached (2.9–20.5+) 8.4 (1.4+–15.2+) mPFS, mo (95% CI) 3.5 (2.1, 4.9) 2.8 (2.1, 3.5) 1-yr PFS, % (95% CI) 21 (14, 28) 6 (3, 12) PD-1 expression NIVO (n) DOC (n) OS HR (95% CI) ≥ 1% 63 56 0.69 (0.45, 1.05) < 1% 54 52 0.58 (0.37, 0.92) ≥ 5% 42 39 0.53 (0.31, 0.89) < 5% 75 69 0.70 (0.47, 1.02) ≥ 10% 36 33 0.50 (0.28, 0.89) < 10% 81 0.70 (0.48, 1.01) ASCO® 2015 - D’après Spiegel D et al., abstr. 8009, actualisé

Étude de phase III, CheckMate 017 comparant en seconde ligne nivolumab et docétaxel dans les cancers épidermoïdes (4) Nivolumab (n = 292) Docétaxel (n = 290) Médiane, mois (IC95) 9,2 (7,3-13,3) 6,0 (5,1-7,3) Événements 86 113 HR = 0,73 ; IC96 : 0,59-0,89 ; p = 0,0015 100 80 60 Taux de SG à 1 an = 42 % Survie globale (%) 40 Nivolumab 20 Taux de SG à 1 an = 24 % Docétaxel 8009 - A phase III study (CheckMate 017) of nivolumab (NIVO; anti-programmed death-1 [PD-1]) vs docetaxel (DOC) in previously treated advanced or metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC).   Session: Immunotherapy in Lung Cancer: A Paradigm Shift Type: Clinical Science Symposium Time: Sunday May 31, 4:30 PM to 6:00 PM Location: E Hall D1 Citation:Abstract: Background: Treatment options are limited for patients (pts) with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC). We report results of a randomized, open-label, global phase III study of NIVO, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, vs DOC in pts with SQ NSCLC and with disease progression (PD) during/after one prior PT-DC regimen. Methods: Pts (N = 272) were randomized 1:1 to receive NIVO 3 mg/kg (n = 135) Q2W or DOC 75 mg/m2(n = 137) Q3W until PD, discontinuation due to toxicity, or other reasons. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), quality of life, and safety. Results:Superior OS was observed with NIVO vs DOC (HR = 0.59; 95% CI: 0.44, 0.79; p = 0.00025). NIVO improved PFS vs DOC (HR = 0.62; 95% CI: 0.47, 0.81; p = 0.0004). ORR was 20% (27/135) for NIVO and 9% (12/137) for DOC (p = 0.0083). OS HRs favored NIVO regardless of PD-L1 expression (Table). Grade 3–4 drug-related AEs occurred in 7% (9/131) of NIVO and 55% (71/129) of DOC pts. No deaths were related to NIVO vs 3 DOC-related deaths. Conclusions: CheckMate 017 met its primary objective, demonstrating superior OS of NIVO vs DOC in pts with advanced, previously treated SQ NSCLC and demonstrated PFS and ORR superiority. Tumor PD-L1 status was neither prognostic nor predictive for efficacy endpoints. The safety profile of NIVO 3 mg/kg Q2W is acceptable and favorable vs DOC. NIVO represents a significant improvement in second-line therapy for SQ NSCLC. Clinical trial information: NCT01642004 NIVO (n = 135) DOC (n = 137) mOS, mo (95% CI) 9.2 (7.3, 13.3) 6.0 (5.1, 7.3) 1-yr OS, % (95% CI) 42 (34, 50) 24 (17, 31) Median duration of response, mo (range) Not Reached (2.9–20.5+) 8.4 (1.4+–15.2+) mPFS, mo (95% CI) 3.5 (2.1, 4.9) 2.8 (2.1, 3.5) 1-yr PFS, % (95% CI) 21 (14, 28) 6 (3, 12) PD-1 expression NIVO (n) DOC (n) OS HR (95% CI) ≥ 1% 63 56 0.69 (0.45, 1.05) < 1% 54 52 0.58 (0.37, 0.92) ≥ 5% 42 39 0.53 (0.31, 0.89) < 5% 75 69 0.70 (0.47, 1.02) ≥ 10% 36 33 0.50 (0.28, 0.89) < 10% 81 0.70 (0.48, 1.01) 3 6 9 12 15 18 21 24 Patients à risque (n) Mois Nivolumab Docétaxel 135 137 113 103 86 68 69 45 52 30 31 14 15 7 7 2 ASCO® 2015 - D’après Spiegel D et al., abstr. 8009, actualisé

Survie sans progresion (%) Étude de phase III, CheckMate 017 comparant en seconde ligne nivolumab et docétaxel dans les cancers épidermoïdes (5) 100 Nivolumab (n = 292) Docétaxel (n = 290) Médiane SSP, mois (IC95) 3,5 (2,1-4,9) 2,8 (2,1-3,5) HR = 0,62 ; IC95 : 0,47-0,81 ; p = 0,0004 80 60 Survie sans progresion (%) 40 Taux de SG à 1 an = 21 % Nivolumab 20 8009 - A phase III study (CheckMate 017) of nivolumab (NIVO; anti-programmed death-1 [PD-1]) vs docetaxel (DOC) in previously treated advanced or metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC).   Session: Immunotherapy in Lung Cancer: A Paradigm Shift Type: Clinical Science Symposium Time: Sunday May 31, 4:30 PM to 6:00 PM Location: E Hall D1 Citation:Abstract: Background: Treatment options are limited for patients (pts) with advanced SQ NSCLC who fail platinum-based doublet chemotherapy (PT-DC). We report results of a randomized, open-label, global phase III study of NIVO, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, vs DOC in pts with SQ NSCLC and with disease progression (PD) during/after one prior PT-DC regimen. Methods: Pts (N = 272) were randomized 1:1 to receive NIVO 3 mg/kg (n = 135) Q2W or DOC 75 mg/m2(n = 137) Q3W until PD, discontinuation due to toxicity, or other reasons. The primary objective was overall survival (OS). Secondary objectives included investigator-assessed objective response rate (ORR; RECIST v1.1), progression-free survival (PFS), efficacy by PD-L1 expression (PD-L1 testing not required for enrollment), quality of life, and safety. Results:Superior OS was observed with NIVO vs DOC (HR = 0.59; 95% CI: 0.44, 0.79; p = 0.00025). NIVO improved PFS vs DOC (HR = 0.62; 95% CI: 0.47, 0.81; p = 0.0004). ORR was 20% (27/135) for NIVO and 9% (12/137) for DOC (p = 0.0083). OS HRs favored NIVO regardless of PD-L1 expression (Table). Grade 3–4 drug-related AEs occurred in 7% (9/131) of NIVO and 55% (71/129) of DOC pts. No deaths were related to NIVO vs 3 DOC-related deaths. Conclusions: CheckMate 017 met its primary objective, demonstrating superior OS of NIVO vs DOC in pts with advanced, previously treated SQ NSCLC and demonstrated PFS and ORR superiority. Tumor PD-L1 status was neither prognostic nor predictive for efficacy endpoints. The safety profile of NIVO 3 mg/kg Q2W is acceptable and favorable vs DOC. NIVO represents a significant improvement in second-line therapy for SQ NSCLC. Clinical trial information: NCT01642004 NIVO (n = 135) DOC (n = 137) mOS, mo (95% CI) 9.2 (7.3, 13.3) 6.0 (5.1, 7.3) 1-yr OS, % (95% CI) 42 (34, 50) 24 (17, 31) Median duration of response, mo (range) Not Reached (2.9–20.5+) 8.4 (1.4+–15.2+) mPFS, mo (95% CI) 3.5 (2.1, 4.9) 2.8 (2.1, 3.5) 1-yr PFS, % (95% CI) 21 (14, 28) 6 (3, 12) PD-1 expression NIVO (n) DOC (n) OS HR (95% CI) ≥ 1% 63 56 0.69 (0.45, 1.05) < 1% 54 52 0.58 (0.37, 0.92) ≥ 5% 42 39 0.53 (0.31, 0.89) < 5% 75 69 0.70 (0.47, 1.02) ≥ 10% 36 33 0.50 (0.28, 0.89) < 10% 81 0.70 (0.48, 1.01) Taux de SG à 1 an = 6,4 % Docétaxel 3 6 9 12 15 18 21 24 Patients à risque (n) Mois Nivolumab Docétaxel 135 137 68 62 48 26 33 9 21 6 15 2 6 1 2 ASCO® 2015 - D’après Spiegel D et al., abstr. 8009, actualisé