NSCLC: CheckMate 057 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

NIVO

doce

292

290

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

Nonsquamous

Stage:

meta

Line of therapy:

L2

Primary
NIVO
doce
HR
p
OS
12.2 mo
9.4 mo
0.73 (0.59-0.89)
0.002
OS @1yr
51%
39%
Secondaries
NIVO
doce
HR
p
OS @18mo
39%
23%
ORR
19%
12%
0.02
PFS
2.3 mo
4.2 mo
0.92 (0.77–1.11)
0.39
PFS @1yr
19%
8%
(all grades, %)
NIVO
doce
p
Any AE gr. 3-4
10%
54%
NA
Fatigue
16
29
NA
Nausea
12
26
NA
Diarrhea
8
23
NA
Peripheral edema
3
10
NA
Anemia
2
20
NA
Alopecia
<1
25
NA
Neutropenia
<1
31
NA
Febrile neutropenia
0
10
NA
Leukopenia
0
10
NA
  • Inclusion
  • Exclusion

- Men & women ≥18 years of age - Subjects with histologically or cytologically documented non-squamous cell NSCLC who present with Stage IIIB/IV disease or recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation therapy for locally advanced disease) and who will receive study therapy as the second or third line of treatment for advanced disease - Disease recurrence or progression during/after one prior platinum doublet-based chemotherapy regimen for advanced or metastatic disease - Measurable disease by Computed tomography (CT)/Magnetic resonance imaging (MRI) per RECIST 1.1 criteria - Eastern Cooperative Oncology Group (ECOG) performance status ≤1 - A formalin-fixed, paraffin-embedded (FFPE) tumor tissue block or unstained slides of tumor sample (archival or recent) must be available for biomarker evaluation. Specimens must be received by the central lab prior to randomization. Biopsy should be excisional, incisional or core needle. Fine needle aspiration is insufficient. Other protocol-defined inclusion/exclusion criteria apply.

- Subjects with untreated central nervous system (CNS) metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic or treated and subjects are neurologically returned to baseline for at least 2 weeks prior to enrollment. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of ≤10mg daily prednisone (or equivalent) - Subjects with carcinomatous meningitis - Subjects with an active or recent history of known or suspected autoimmune disease. Subjects with Type 1 diabetes mellitus, hypothyroidism only requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll - Subjects with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of randomization - Prior therapy with anti-programmed death-1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), anti-programmed cell death ligand 2 (anti-PD-L2), anti-cluster of differentiation 137 (anti-CD137), or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody (including Ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) - Prior treatment with Docetaxel - Treatment with any investigational agent within 14 days of first administration of study treatment. Other protocol-defined inclusion/exclusion criteria apply.

Characteristics
NIVO
doce
Agedc-comma sex
Median age (range) yr
61 (37-84)
64 (21-85)
≥75 yr
20 (7)
23 (8)
Male - no.(%)
151 (52)
168 (58)
Race - no.(%)
White
267 (91)
266 (92)
Asian
9 (3)
8 (3)
Black
7 (2)
9 (3)
Other
9 (3)
7 (2)
ECOG PS - no.(%)
0
84 (29)
95 (33)
1
208 (71)
194 (67)
Not reported
0
1 (<1)
Disease stage - no.(%)
IIIB
20 (7)
24 (8)
IV
272 (93)
266 (92)
Smoking status - no.(%)
Current or former smoker
231 (79)
227 (78)
Never smoked
58 (20)
60 (21)
Unknown
3 (1)
3 (1)
Mutation status - no.(%)
Positive EGFR mutation
44 (15)
38 (13)
Positive ALK translocation
13 (4)
8 (3)
Positive KRAS mutation
28 (10)
34 (12)
No. of prior systemic regimens - no.(%)
1
256 (88)
259 (89)
2
35 (12)
31 (11)
Other
1 (<1)
0
Type of prior systemic therapy - no.(%)
Platinum-based therapy
292 (100)
290 (100)
ALK inhibitor
1 (<1)
2 (1)
EGFR tyrosine kinase inhibitor
29 (10)
24 (8)
Prior maintenance therapy
122 (42)
111 (38)
Best response to most recent prior systemic regimen - no.(%)
Complete or partial response
73 (25)
68 (23)
Stable disease
103 (35)
96 (33)
Progressive disease
111 (38)
116 (40)
Unknown or not reported
5 (2)
10 (3)
PD-L1 expression level - no.(%)
<1%
108 (47)
101 (45)
≥1%
123 (53)
123 (55)
<5%
136 (59)
138 (62)
≥5%
95 (41)
86 (38)
PD-L1 expression level - no.(%)
<10%
145 (63)
145 (65)
≥10%
86 (37)
79 (35)
Not quantifiable
61 (21)
66 (23)
Ad-hoc:
no.pts inv.
no.pts comp.
NIVO
doce
HR
p
Time to response
292
290
2.1 mo
2.6 mo
Duration of response
292
290
17.2 mo
5.6 mo
ORR
292
290
19%
12%
0.02
  • OS
  • OS @1yr
analisys of OS
NIVO
doce
HR (95% CI)
Previous maintenance therapy
Yes (n=233)
0.80 (0.58–1.10)
No (n=349)
0.73 (0.57–0.93)
Line of therapy
Second line (n=515))
0.69 (0.56–0.85)
Third line (n=66)
1.34 (0.73–2.43)
ECOG
0 (n=179)
0.64 (0.44–0.93)
1 (n=402)
0.80 (0.63–1.00)
Smoking status
Current or former smoker (n=458)
0.70 (0.56–0.86)
Never smoked (n=118)
1.02 (0.64–1.61)
EGFR mutation status
Positive (n=82)
1.18 (0.69–2.00)
Not detected (n=340)
0.66 (0.51–0.86)
KRAS mutation status
Positive (n=62)
0.52 (0.29–0.95)
Not detected (n=123)
0.98 (0.66–1.48)
Age
<65 yr (n=339)
0.81 (0.62–1.04)
≥65 to <75 yr (n=200)
0.63 (0.45–0.89)
Sex
Male (319)
0.73 (0.56–0.96)
Female (263)
0.78 (0.58–1.04)
analisys of OS @1yr
NIVO
doce
HR (95% CI)