NSCLC: IMpower110 trial

Abbreviations

No EU-CTR

  • IMpower110 references
    2020-10-01
    Roy S. Herbst
    Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC
Investigated (inv)
Comparator (comp)

ATEZ

chemo

277

277

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

na, Nonsquamous, Squamous

Stage:

meta

Line of therapy:

L1

Primary
ATEZ
chemo
HR
p
OS (PD-L1 high; EGFR, ALK WT)
20.2 mo
13.1 mo
0.59 (0.40-0.89)
0.01
PFS TMB
Secondaries
ATEZ
chemo
HR
p
PFS (PD-L1 high; EGFRdc-comma ALK WT)
8.1 mo.
5.0 mo.
0.63 (0.45-0.88)
ORR (PD-L1 high; EGFRdc-comma ALK WT)
38.3%
28.6%
OS (PD-L1 high or interm)
18.2 mo
14.9 mo
0.72 (0.52-0.99)
0.04
(all grades, %)
ATEZ
chemo
p
Any AE grade 3-4
30.1
52.5
NA
Anemia
15.4
47.5
NA
Nausea
13.6
33.8
NA
Constipation
12.2
21.7
NA
Hyponatremia
5.9
4.6
NA
Pneumonia
4.9
6.5
NA
Hyperkalemia
4.2
3.0
NA
Thrombocytopenia
2.4
16.7
NA
Neutropenia
1.4
28.1
NA
Febrile neutropenia
0
3.4
NA
Hypertension
1.7
3.4
NA
Leukopenia
1.0
8.0
NA
Melena
0.3
0.0
NA
Pancytopenia
0.3
1.5
NA
  • Inclusion
  • Exclusion

- Histologically or cytologically confirmed, Stage IV non-squamous or squamous NSCLC - No prior treatment for Stage IV non-squamous or squamous NSCLC. Participant known to have a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene are excluded from the study - Tumor PD-L1 expression as determined by immunohistochemistry (IHC) assay of archival tumor tissue or tissue obtained at screening - Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 - Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) - Adequate hematologic and end-organ function.

- Known sensitizing mutation in the EGFR gene or ALK fusion oncogene - Active or untreated central nervous system (CNS) metastases as determined by Computed Tomography (CT) or magnetic resonance imaging (MRI) evaluation - Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome - Pregnant or lactating women - History of autoimmune disease - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. - History of radiation pneumonitis in the radiation field (fibrosis) is permitted - Positive test for Human Immunodeficiency Virus (HIV) - Active hepatitis B or hepatitis C - Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, anti PD1, and anti-PD-L1 therapeutic antibody - Severe infection within 4 weeks prior to randomization - Significant history of cardiovascular disease.

Characteristics
ATEZ
chemo
Agedc-comma sex
Median age (range)dc-comma yr
64 (30–81)
65 (30–87)
Male - no.(%)
196 (70.8)
193 (69.7)
Race - no.(%)
White
227 (81.9)
240 (86.6)
Asian
45 (16.2)
30 (10.8)
Black
2 (0.7)
2 (0.7)
Unknown
2 (0.7)
5 (1.8)
ECOG - no.(%)
0
97 (35.0)
102 (36.8)
1
180 (65.0)
175 (63.2)
History of tobacco use - no.(%)
Never
37 (13.4)
35 (12.6)
Current
74 (26.7)
81 (29.2)
Previous
166 (59.9)
161 (58.1)
Histologic type at diagnosis - no.(%)
Nonsquamous
192 (69.3)
193 (69.7)
Squamous
85 (30.7)
84 (30.3)
Geographic region - no.(%)
Europe
209 (75.5)
225 (81.2)
Asia Pacific
44 (15.9)
29 (10.5)
South America
15 (5.4)
16 (5.8)
North America
9 (3.2)
7 (2.5)
Ad-hoc:
no.pts inv.
no.pts comp.
ATEZ
chemo
HR
p
OS any PD-L1
277
277
17.5 mo
14.1 mo
0.83 (0.65–1.07)
  • OS (PD-L1 high; EGFR, ALK WT)
  • PFS TMB
analisys of OS (PD-L1 high; EGFR, ALK WT)
ATEZ
chemo
HR (95% CI)
Age
<65 yr
NE
13.1
0.59 (0.34-1.04)
65-74 yr
17.8 mo
10.4
0.63 (0.34-1.19)
Sex
Male
23.1 mo
13.1 mo
0.57 (0.35-0.93)
Female
17.8 mo
14.1 mo
0.69 (0.34-1.39)
Race
White
17.8 mo
13.1 mo
0.67 (0.44-1.03)
Asian
NE
14.1 mo
0.38 (0.13-1.13)
ECOG
0
NE
15.7 mo
0.42 (0.20-0.92)
1
16.5 mo
13.1 mo
0.69 (0.43-1.10)
History of tobacco use
Current
NE
10.2 mo
0.35 (0.14-0.88)
Previous
23.1 mo
13.1 mo
0.60 (0.36-1.00)
Histology
Nonsquamous
20.2 mo
10.5 mo
0.62 (0.40-0.96)
Squamous
NE
15.2 mo
0.56 (0.23-1.37)
Geographic region
Europe
17.8 mo
13.1 mo
0.81 (0.52-1.27)
Asia Pacific
NE
12.3 mo
0.35 (0.12-1.04)
Geographic region
Sputh America
NE
5.9 mo
0.17 (0.02-1.49)
North America
NE
11.4 mo
<0.01 (0.0-NE)
analisys of PFS TMB
ATEZ
chemo
HR (95% CI)
PD-L1 expression
Any PD-L1 expression
5.7 mo
5.5 mo
0.77 (0.63–0.94)
Could be evaluated for blood-based TMB
No
9.3 mo
5.7 mo
0.53 (0.36–0.79)
Yes
5.5 mo
5.4 mo
0.88 (0.70–1.11)
Blood-based TMB
≥10
5.5 mo
4.3 mo
0.74 (0.53–1.05)
≥16
6.8 mo
4.4 mo
0.55 (0.33–0.92)
Blood-based TMB
≥20
6.8 mo
5.2 mo
0.56 (0.30–1.06)
<10
5.5 mo
5.7 mo
1.03 (0.76–1.39)
Blood-based TMB
<16
4.5 mo
5.5 mo
1.00 (0.78–1.29)
<20
4.9 mo
5.4 mo
0.95 (0.74–1.21)