Immunotherapy advances in lung cancer

Recent Developments With Immunotherapy for
Patients With Advanced NSCLC
Alok Gupta

3
Current Treatment Overview of Advanced or Metastatic NSCLC
Chemotherapy Targeted Therapy Immune Checkpoint Inhibitors
Standard of Care
• Used across all lines of therapy1
• Commonly used agents: (1L) platinum-based
chemotherapy, (2L) single-agent docetaxel,
pemetrexed, gemcitabine1,2
• Backbone of therapy for patients with lung
cancer3
EGFR/ALK+ Patients
• Mutational status rates and testing vary by
market/region
• Commonly used agents: erlotinib, gefitinib,
afatinib (EGFR+), crizotinib, ceritinib (ALK+)1,4
• Improved outcomes in patients with
mutations5–7
1L PD-L1 High Expressing Patients
2L+ All-comers or PD-L1+ Patients
• Indications/approvals vary by market/region
• Agents: (1L and 2L+) pembrolizumab (PD-L1
expression ≥50% and ≥1%, respectively), (2L+)
nivolumab and atezolizumab (all comers)8–10
• New to market; target immunosuppressive
mechanisms11
Mutation
M
G1
S
G2 G0
G1/S
Checkpoint
G2/M
Checkpoint
1L = first line; 2L = second line; ALK = anaplastic lymphoma kinase; EGFR = epidermal growth factor receptor; NSCLC = non–small cell lung cancer; PD-L1 = programmed death ligand 1.
Cell cycle image reprinted with permission from Samarasinghe B. The hallmarks of cancer: 2 – insensitivity to antigrowth signals. Scientific American website. http://blogs.scientificamerican.com/guest-blog/the-hallmarks-of-cancer-2-
insensitivity-to-antigrowth-signals. Immune checkpoint inhibitors image adapted from Chen DS et al. Immunity. 2013;39(1):1–10. Reprinted with permission from Elsevier.
1. World Health Organization Expert Committees: 2014 Review of Cancer Medicines on the WHO List of Essential Medicines: Non–Small Cell Lung Cancer. http://www.who.int/selection_medicines/committees
/expert/20/applications/NonSmallCellLungCancer.pdf?ua=1. Accessed 5 April 2017. 2. Davies J et al. PLoS One. 2017;12(4):e0175679. 3. Carrizosa DR et al. Oncology (Williston Park). 2013;27(5):396–404. 4. Holla VR et al. Cold Spring Harb Mol
Case Stud. 2017; 3(1):a001115. 5. Kwak EL et al. N Engl J Med. 2010;363(18):1693–1703. 6. Maemondo M et al. N Engl J Med. 2010;362(25):2380–2388. 7. Zhou C et al. Lancet Oncol. 2011;12(8):735–742. 8. Keytruda Prescribing Information India,
2018 9. OPDIVO US Prescribing Information. Princeton, NJ: Bristol-Myers Squibb; January 2016. 10. TCENTRIQ US Prescribing Information. South San Francisco, CA: Genentech, Inc: October 2016. 11. Garon EB. Semin Oncol. 2015;42(Suppl
2):S11–S18.

5
Antitumor Immune Response in Advanced or Metastatic NSCLC
• The body’s immune response can detect and destroy tumor cells through activated T cells
and other mechanisms.1
• Tumor cells express multiple antigens that are not expressed in normal tissue.2
T-cell–mediated Immune Response1,2
NSCLC = non‒small cell lung cancer.
Image adapted from Chen DS et al. Immunity. 2013;39(1):1–10. Reprinted with permission from Elsevier.
1. May KF Jr et al. In: Prendergast GC et al. Cancer Immunotherapy. 2nd ed. Philadelphia, PA: Elsevier; 2013:101–113. 2. Chen DS et al. Immunity. 2013;39(1):1–10.
Tumor cell
Tumor-specific antigens
Dendritic cell
Naïve cytotoxic
T cell
Tumor cellActivated cytotoxic
T cell
Antitumor effector mechanisms

6
Abs = antibodies; BTLA = B and T lymphocyte attenuator; CD = cluster of differentiation; CTLA-4 = cytotoxic T-lymphocyte–associated antigen 4; GITR = glucocorticoid induced tumor necrosis factor-related protein; HVEM = herpes virus entry
mediator; LAG-3 = lymphocyte activation gene 3; PD-1 = programmed death receptor-1;
TIM-3 = T-cell immunoglobulin domain and mucin domain-3; VISTA = V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation.
Image reprinted with permission from Mellman I et al. Nature. 2011;480(7378):480–489.
1. Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.
2. Mellman I et al. Nature. 2011;480(7378):480–489.
Tumors Exploit Immune Checkpoint Pathways as One Mechanism of
Immune Evasion
• Normal immune checkpoint pathway
= elaborate series of cellular
interactions that prevent excessive T-
cell activity.1
• T-cell responses are regulated by a
number of activating and inhibitory
interactions.1
Immune Checkpoint Receptors2

In Advanced or Metastatic NSCLC, the PD-1 Pathway May Be Exploited
to Evade the Immune Response1,2
APC = antigen-presenting cell; MHC = major histocompatibility complex; NSCLC = non‒small cell lung cancer; PD-1 = programmed death receptor-1;
PD-L1 = programmed death ligand 1; PD-L2 = programmed death ligand 2; TCR = T-cell receptor.
Image adapted with permission from Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.
1. Keytruda Prescribing Information India, 2018 2. Pardoll DM. Nat Rev Cancer. 2012;12(4):252–264.
• Emerging research has identified PD-1 as a key immune checkpoint pathway involved in inhibiting the T-
cell–mediated immune response.
• Tumor cells can downregulate T-cell activity by exploiting the PD-1 checkpoint pathway through
expression of the PD-1 ligands, PD‐L1 and PD‐L2.
• PD-L1 and PD-L2 engage the PD-1 receptor on T cells to inactivate them, which may allow tumor cells to
evade the immune response.
Antigen
MHCTCR
Activated cytotoxic
T cell
Tumor cell/APC
PD-L2
PD-L1
PD-1
Antigen
MHCTCR
Inactivated cytotoxic
T cell
PD-1
PD-L2
PD-L1
Tumor cell/APC

Phase III KEYNOTE-024: Pembrolizumab vs CT as First-
line Therapy for Advanced NSCLC With PD-L1 ≥ 50%
 Primary endpoint: PFS
 Secondary endpoints: ORR, OS, and safety
Patients with stage IV NSCLC and
ECOG PS 0/1, no previous systemic
therapy, no actionable EGFR/ALK
mutations, and PD-L1 TPS ≥ 50%*
(N = 305)
Pembrolizumab 200 mg IV Q3W
for up to 35 cycles
(n = 154)
Histology-based Chemotherapy†
for up to 6 cycles
(n = 151)
Until PD or
unacceptable toxicity
Stratified by ECOG PS (0 vs 1), histology (squamous
vs nonsquamous), and enrollment region
Until PD (crossover to
pembrolizumab allowed
if safety criteria met)
*≥ 50% tumor cell staining using 22C3 companion diagnostic IHC assay.
†Investigator’s choice of: pem + carbo or cis; pac + carbo; gem + carbo or cis. Pem-containing regimens only for nonsquamous
histology; these patients could receive pem maintenance treatment.
Slide credit: clinicaloptions.comReck M, et al. N Engl J Med. 2016;375:1823-1833.

KEYNOTE-024: Survival
Slide credit: clinicaloptions.com
PFS2[1]
Mos
Patients at Risk, n
100
80
60
40
20
0
PFS2(%)
0 63 9 12 1815 21 24
154
151
134
121
112
99
96
64
90
56
71
36
40
18
16
6
3
1
59.7%
38.5% 51.0%
24.6%
mPFS: 10.3 vs 6.0 mos[2]
mPFS2: 18.3 vs 8.4 mos
HR: 0.54 (P < .001)
24
4
4
OS[1]
Mos
100
80
60
40
20
0
OS(%)
0 63 9 12 1815 21
154
151
136
123
121
107
112
88
106
79
88
64
57
35
20
15
70.3%
54.8% 61.0%
43.0%
mOS: NR vs 14.5 mos
HR: 0.63 (P = .003)
1. Brahmer JR, et al. ASCO 2017. Abstract 9000. 2. Reck M, et al. N Engl J Med. 2016;375:1823-1833.
Pembrolizumab
Chemotherapy
Patients at Risk, n

Recent Developments With Immunotherapy for
Patients With Advanced NSCLC

Why Combine Chemotherapy With Immunotherapy?
 Cytotoxic agents enhance antigen presentation and immunogenic cell
death[1]
 Chemotherapy disrupts immune evasion mechanisms in the tumor
microenvironment[2,3]
 Dose, schedule, and drug dependent[4,5]
1. Zitvogel L, et al. Immunity. 2013;39:74-88. 2. Mouw KW, et al. Cancer Discov. 2017;7:675-693.
3. Fukumura D, et al. Nat Rev Clin Oncol. 2018;15:325-340. 4. Emens LA, et al. Curr Opin Mol Ther. 2001;3:77-84.
5. Chen G, Emens LA. Cancer Immunol Immunother. 2013;62:203-216.

 Primary endpoint: PFS by RECIST v1.1 (BICR), OS
 Secondary endpoints: ORR and DoR by RECIST v1.1 (BICR), safety
Phase III KEYNOTE-407: CT ± Pembrolizumab in
Untreated Metastatic Squamous NSCLC
Paz-Ares LG, et al. ASCO 2018. Abstract 105. ClinicalTrials.gov. NCT02775435. Slide credit: clinicaloptions.com
Pembrolizumab + Carboplatin +
Paclitaxel or nab-Paclitaxel
3-wk cycle x 4
(n = 278)
Patients with untreated stage IV
squamous NSCLC, ECOG PS 0/1,
available tumor biopsy for PD-L1
assessment, no brain mets, and
no pneumonitis requiring
systemic steroids
(N = 559)
Stratified by PD-L1 TPS (< 1% vs ≥ 1%), taxane (paclitaxel
vs nab-paclitaxel), region (east Asia vs other)
Carboplatin AUC 6 Q3W, nab-paclitaxel 100 mg/m2 QW, paclitaxel 200 mg/m2 Q3W, pembrolizumab 200 mg Q3W.
*Upon confirmation of PD by BICR and fulfillment of safety criteria, optional crossover could occur during combination or monotherapy.
Placebo + Carboplatin +
Paclitaxel or nab-Paclitaxel
3-wk cycle x 4
(n = 281)
Pembrolizumab
up to 31 cycles
Placebo
up to 31 cycles
Pembrolizumab
up to 35 cycles
Crossover
allowed*
PD

KEYNOTE-407: PFS by RECIST v1.1 (BICR) in ITT
Population
 ORR: 58.4% vs 35%, P = .0004, pembro + chemo vs chemo, respectively.
Paz-Ares LG, et al. ASCO 2018. Abstract 105. Slide credit: clinicaloptions.com
Mos
Patients at Risk, n
PFS(%)
Median PFS, Mos (95% CI)
6.4 (6.2-8.3)
4.8 (4.3-5.7)
100
80
60
40
20
0
0 3 6 9 12 15 18 21
Pembro + Chemo
Chemo
54.7
70.1
0.56
(0.45-0.70)
< .0001
Events, % HR (95% CI) P Value
278
281
223
190
142
90
57
26
23
12
5
4
0
0
0
0

505050
KEYNOTE-407: PFS by PD-L1 Expression Level
TPS < 1% TPS 1% to 49% TPS ≥ 50%
Mos
PFS(%)
210 3 6 9 12 15 18
100
90
80
70
60
40
30
20
10
0
6.3 (6.1-6.5)
5.3 (4.4-6.2)
Events, % HR (95% CI)
Pembro + chemo 57.9 0.68 (0.47-0.98)
Placebo + chemo 67.7
Patients at Risk, n
95
99
78
71
48
35
16
11
5
6
0
1
0
0
0
0
BICR, blinded, independent central review. Data cutoff date: Apr 3, 2018.
Mos
PFS(%)
210 3 6 9 12 15 18
100
90
80
70
60
40
30
20
10
0
7.2 (6.0-11.4)
5.2 (4.2-6.2)
103
104
79
79
49
40
26
8
13
4
5
1
0
0
0
0
52.4 0.56 (0.39-0.80)
70.2
Mos
PFS(%)
210 3 6 9 12 15 18
100
90
80
70
60
40
30
20
10
0
8.0 (6.1-10.3)
4.2 (2.8-4.6)
73
73
60
38
41
13
12
5
4
2
0
2
0
0
0
0
53.4 0.37 (0.24-0.58)
75.3
Patients at Risk, n Patients at Risk, n

KEYNOTE-407: OS in ITT Population
Mos
Patients at Risk, n
OS(%)
Median OS, Mos (95% CI)
15.9 (13.2-NE)
11.3 (9.5-14.8)
100
80
60
40
20
0
0 3 6 9 12 15 18 21
Pembro + Chemo
Chemo
30.6
42.7
0.64
(0.49-0.85)
.0008
Events, % HR (95% CI) P Value
278
281
256
246
188
175
124
93
62
45
17
16
2
4
0
0

40
KEYNOTE-407: OS by PD-L1 Expression Level (Second
Interim Analysis)
50 5050
TPS < 1% TPS 1% to 49% TPS ≥ 50%
Mos
OS(%)
210 3 6 9 12 15 18
100
90
80
70
60
40
30
20
10
0
15.9 (13.1-NE)
10.2 (8.6-13.8)
Pembro + chemo 30.5 0.61 (0.38-0.98)
Placebo + chemo 44.4
95
99
78
92
62
63
41
32
20
14
5
4
1
1
0
0
Data cutoff date: Apr 3, 2018.
Mos
OS(%)
210 3 6 9 12 15 18
100
90
80
70
60
40
30
20
10
0
14.0 (12.8-NE)
11.6 (8.9-17.2)
103
104
95
90
68
66
50
37
25
21
9
6
1
0
0
0
30.1 0.57 (0.36-0.90)
43.3
Mos
OS(%)
210 3 6 9 12 15 18
100
90
80
70
60
30
20
10
0
NR (11.3-NE)
NR (7.4-NE)
73
73
66
60
53
42
28
21
15
9
3
5
0
2
0
0
31.5 0.64 (0.37-1.10)
41.1
Patients at Risk, n Patients at Risk, n Patients at Risk, n

Phase III IMpower131: CT ± Atezolizumab in Untreated
Metastatic Squamous NSCLC
 Coprimary endpoints: investigator-assessed PFS per RECIST v1.1, OS (ITT)
 Secondary endpoints: PFS, OS in PD-L1 subgroups; ORR, DoR, safety
Jotte RM, et al. ASCO 2018. Abstract LBA9000. Slide credit: clinicaloptions.com
Patients with
stage IV squamous
NSCLC*; no prior CT;
ECOG PS 0/1;
any PD-L1 status†
(N = 1021)
Atezolizumab 1200 mg IV Q3W +
Carboplatin/Paclitaxel‡ for 4-6 cycles
(n = 338)
Carboplatin/nab-Paclitaxel‡
for 4-6 cycles
(n = 340)
Carboplatin/nab-Paclitaxel‡ for 4-6 cycles
(n = 343)
Until PD
or loss of
clinical benefit
Stratified by sex; PD-L1 expression;
liver metastases
Atezolizumab
Atezolizumab
BSC Until PD
*Patients with EGFR or ALK aberrations must have PD or intolerance to ≥ 1 targeted tx. †PD-L1 assessed by SP142 IHC assay.
‡Carboplatin AUC 6 IV Q3W; nab-paclitaxel 100 mg/m2 IV QW; paclitaxel 200 mg/m2 IV Q3W.
Maintenance
(no crossover allowed)

IMpower131: Survival Outcomes in ITT Populations
(Coprimary Endpoints)
 PD-L1 high: median OS, 23.6 vs 14.1 mos (HR: 0.56; 95% CI: 0.32-0.99); 12-mo OS,
67% vs 52%; 24-mo OS, 47% vs 30%
Jotte RM, et al. ASCO 2018. Abstract LBA9000. Slide credit: clinicaloptions.com
Atezolizumab +
Carbo/nab-Pac
(n = 343)
Carbo/nab-Pac
(n = 340)
Median PFS,
mos (95% CI)
6.3
(5.7-7.1)
5.6
(5.5-5.7)
Mos
12.0%
24.7%
12-mo PFS
PFS(%)
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 101112131415161718192021222324252627282930
Atezolizumab +
Carbo/nab-Pac
(n = 343)
Carbo/nab-Pac
(n = 340)
Median OS,
Mos (95% CI)
14.0
(12.0-17.0)
13.9
(12.3-16.4)
100
HR: 0.71 (95% CI: 0.60-0.85; P = .0001)
Minimum follow-up: 9.8 mos
Median follow-up: 17.1 mos
55.6%
56.9%
31.9%
12-mo OS
24.1%
24-mo OS
OS(%)
0
20
40
60
80
HR: 0.96 (95% CI: 0.78-1.18; P = .6931)
Mos
320 1 2 3 4 5 6 7 8 9 10111213141516171819202122232425262728293031

IMpower131: Investigator-Assessed PFS by PD-L1
Slide credit: clinicaloptions.comJotte RM, et al. ASCO 2018. Abstract LBA9000.
HR: 0.70
(95% CI: 0.53-0.92)
HR: 0.44
(95% CI: 0.27-0.71)
HR: 0.81
(95% CI: 0.64-1.03)
Atezolizumab +
Carbo/nab-Pac
Carbo/
nab-Pac
Atezolizumab +
Carbo/nab-Pac
Carbo/
nab-Pac
Atezolizumab +
Carbo/nab-Pac
Carbo/
nab-Pac
Patients, n 53 48 129 121 160 171
12-mo PFS, % 48 20 20 9 20 12
Median PFS, mos 10.1 5.5 6.0 5.6 5.7 5.6
PD-L1 High (TC3 or IC3) PD-L1 Low (TC1/2 or IC1/2) PD-L1 Negative (TC0 and IC0)
28
0
20
40
60
80
100
0 2 4 6 8 1012 18
Mos
PFS(%)
1416 20 22 2426
0
20
40
60
80
0 2 4 6 8 10 12 18
PFS(%)
14 16 20 22 24
100
28
0
20
40
60
80
100
0 2 4 6 8 10 12 18
PFS(%)
14 16 20 22 24 26 30
Mos Mos

28
IMpower131: Interim OS by PD-L1
Slide credit: clinicaloptions.comJotte RM, et al. ASCO 2018. Abstract LBA9000.
Atezolizumab +
Carbo/nab-Pac
Carbo/
nab-Pac
Atezolizumab +
Carbo/nab-Pac
Carbo/
nab-Pac
Atezolizumab +
Carbo/nab-Pac
Carbo/
nab-Pac
Patients, n 53 48 129 121 160 171
12-mo OS, % 67 52 54 64 53 53
24-mo OS, % 47 30 28 37 30 16
Median OS, mos 23.6 14.1 12.4 16.6 13.8 12.5
PD-L1 High (TC3 or IC3) PD-L1 Low (TC1/2 or IC1/2) PD-L1 Negative (TC0 and IC0)
0
20
40
60
80
100
0 2 4 6 8 1012 18
Mos
OS(%)
HR: 0.56
(95% CI: 0.32-0.99)
1416 20 22 2426
0
20
40
60
80
0 2 4 6 8 1012 18
OS(%)
HR: 1.34
(95% CI: 0.95-1.90)
1416 20 22 2426
100
28
0
20
40
60
80
100
0 2 4 6 8 1012 18
OS(%)
HR: 0.86
(95% CI: 0.65-1.15)
1416 202224 26 3032
Mos Mos

Phase III KEYNOTE-189: First-line Pembrolizumab + CT vs
CT in Stage IV Nonsquamous NSCLC
Patients with stage IV
nonsquamous NSCLC and
ECOG PS 0/1,
any PD-L1 status,
no actionable
EGFR/ALK mutations
(N = 616)
Pembrolizumab 200 mg Q3W +
Plt/pemetrexed Q3W
(n = 410)
Placebo Q3W +
Plt/pemetrexed Q3W
(n = 206)
4 cycles
Pembrolizumab* +
Pemetrexed
Q3W
Placebo* +
Pemetrexed
Q3W
Stratified by PD-L1 TPS (≥ 1% vs < 1%),
platinum agent (carboplatin vs cisplatin),
smoking history (never vs former/current)
Until PD or
unacceptable
toxicity;
crossover from
placebo allowed
*Up to total of 35 cycles.
No PD
No PD
Baseline PD-L1 TPS, % < 1% 1% to 49% ≥ 50% Not estimable
Pembro + chemotherapy 31.0 31.2 32.2 5.6
Placebo + chemotherapy 30.6 28.2 34.0 7.3
Slide credit: clinicaloptions.comGandhi L, et al. N Engl J Med. 2018;378:2078-2092.

Median
PFS, Mos
Pembro + CT 8.8
Pbo + CT 4.9
KEYNOTE-189: Survival
PFS OS
0
20
40
60
80
100
0 3 6 9 12 15 18 21
Mos
PFS(%)
410
206
322
141
256
80
149
40
60
16
17
3
5
1
0
0
HR: 0.52 (95% CI: 0.43-0.64; P < .001)
Patients at
Risk, n
Pembro + CT
Pbo + CT
0
20
40
60
80
100
0 3 6 9 12 15 18 21
Mos
OS(%)
410
206
377
183
347
149
278
104
163
59
71
25
18
8
0
0
HR: 0.49 (95% CI: 0.38-0.64; P < .001)
Median
OS, Mos
Pembro + CT NR
Pbo + CT 11.3

KEYNOTE-189: OS by PD-L1 TPS
TPS < 1% TPS ≥ 50%TPS 1% to 49%
0
20
40
60
80
100
0 3 6 9 12 15 18 21
Mos
OS(%)
127
63
113
54
104
45
79
32
42
21
20
6
6
1
0
0
HR: 0.59
(95% CI: 0.38-0.92)
Pembro + CT
Pbo + CT
Patients at
Risk, n
Pembro + CT
Pbo + CT
128
58
119
54
108
47
84
32
52
17
21
5
5
2
0
0
HR: 0.55
(95% CI: 0.34-0.90)
Pembro + CT
Pbo + CT
132
70
122
64
114
50
96
35
56
19
25
13
6
4
0
0
HR: 0.42
(95% CI: 0.26-0.68)
Pembro + CT
Pbo + CT
0
20
40
60
80
100
0 3 6 9 12 15 18 21
0
20
40
60
80
100
0 3 6 9 12 15 18 21
Mos Mos

KEYNOTE-189: PFS by PD-L1 TPS
TPS < 1% TPS ≥ 50%TPS 1% to 49%
0
20
40
60
80
100
0 3 6 9 12 15 18 21
Mos
PFS(%)
127
63
88
44
60
27
31
16
12
4
3
0
2
0
0
0
HR: 0.75
(95% CI: 0.53-1.05)
Patients at Risk, n
Pembro + CT
Pbo + CT
128
58
101
44
84
23
47
11
21
6
6
1
2
0
0
0
HR: 0.55
(95% CI: 0.37-0.81)
132
70
112
43
95
26
60
11
23
5
7
2
1
1
0
0
HR: 0.36
(95% CI: 0.25-0.52)
0
20
40
60
80
100
0 3 6 9 12 15 18 21
0
20
40
60
80
100
0 3 6 9 12 15 18 21
Mos Mos
Pembro + CT
Pbo + CT
Pembro + CT
Pbo + CT
Pembro + CT
Pbo + CT
Gandhi L, et al. N Engl J Med. 2018;378:2078-2092.

Additive Toxicity With Chemotherapy in NSCLC
KEYNOTE 024 KEYNOTE 189
Slide credit: clinicaloptions.com1. Reck M, et al. N Engl J Med. 2016;375:1823-1833. 2. Gandhi L, et al. N Engl J Med. 2018;378:2078-2092.
KEYNOTE-189[2]KEYNOTE-024[1]
Treatment-Related
AE, %
Pembro
(n = 154)
Chemo
(n = 150)
Any Gr Gr ≥ 3 Any Gr Gr ≥ 3
Any 73.4 26.6 90.0 53.3
Anemia 5.2 1.9 44.0 19.3
Nausea 9.7 0 43.3 2.0
Fatigue 10.4 1.3 28.7 3.3
Neutropenia 0.6 0 22.7 13.3
Vomiting 2.6 0.6 20.0 0.7
Diarrhea 14.3 3.9 13.3 1.3
Thrombocytopenia 0 0 11.3 5.3
Pyrexia 10.4 0 5.3 0
Immune mediated 29.2 9.7 4.7 0.7
Any-Cause AE, %
Pembro + Chemo
(n = 405)
Chemo
(n = 202)
Any Gr Gr ≥ 3 Any Gr Gr ≥ 3
Any 99.8 67.2 99.0 65.8
Anemia 46.2 16.3 46.5 15.3
Nausea 55.6 3.5 52.0 3.5
Fatigue 40.7 5.7 38.1 2.5
Neutropenia 27.2 15.8 24.3 11.9
Vomiting 24.2 3.7 23.3 3.0
Diarrhea 30.9 5.2 21.3 3.0
Thrombocytopenia 18.0 7.9 14.4 6.9
Pyrexia 19.5 0.2 14.9 0
Immune mediated 22.7 8.9 11.9 4.5

IMpower132 Phase III Study Design: First-line Atezo +
Carboplatin/ Cisplatin + Pemetrexed in Stage IV NSCLC
 Coprimary endpoints: Investigator-assessed PFS and OS
 Secondary endpoints: Investigator-assessed ORR and DoR, patient-reported outcomes, safety
 Exploratory analyses: clinical and biomarker subgroups
Patients with stage IV
nonsquamous NSCLC
without EGFR or ALK
alterations and no prior
chemotherapy
(N = 578)
Maintenance
until PD or loss of
clinical benefit
Atezolizumab 1200 mg +
Carboplatin AUC 6 or
Cisplatin 75 mg/m2 +
Pemetrexed 500 mg/m2
Q3W x 4 or 6 cycles
(n = 292)
Carboplatin AUC 6 or
Cisplatin 75 mg/m2 +
Pemetrexed 500 mg/m2
Q3W x 4 or 6 cycles
(n = 286)
Stratified by sex, smoking status,
ECOG PS (0 vs 1), chemotherapy regimen
Atezolizumab +
Pemetrexed
4 or 6 cycles
Pemetrexed
4 or 6 cycles
Induction Maintenance
Papadimitrakopoulou VA, et al. WCLC 2018. Abstract OA05.07.

23
IMpower132: PFS, ORR, DoR
Slide credit: clinicaloptions.comPapadimitrakopoulou VA, et al. WCLC 2018. Abstract OA05.07.
Minimum follow-up: 11.7 mos
Median follow-up: 14.8 mos
Outcome Atezolizumab,
Platinum,
Pemetrexed
(n = 292)
Platinum,
Pemetrexed
(n = 286)
PFS, %
 6 mos 59.1 40.9
 12 mos 33.7 17.0
ORR, % 47 32
 CR 2 1
 PR 45 32
Median DoR, mos 10.1 7.2
Median OS, mos 18.1 13.6
Atezo + chemo
Chemo
7.6
5.2
0.60
(95% CI: 0.49-0.72)
< .0001
Median
PFS, Mos HR (95% CI) P Value
APP
PP
100
90
80
70
60
50
40
30
20
10
0
PFS(%)
Mos
0 1 2 3 4 5 6 7 8 9 10111213141516171819202122
Patients at Risk, n
APP
PP
292
286
2280
273
260
236
231
195
224
178
19
142
169
115
149
98
140
87
120
72
110
59
109
53
88
44
48
15
43
11
31
6
26
6
11
3
10
3
274
39

Phase III IMpower150: Atezo + CT ± Bev vs CT + Bev in
Untreated Advanced Nonsquamous NSCLC
 Coprimary endpoints: investigator-assessed PFS and OS
Patients with stage IV or
recurrent metastatic
nonsquamous NSCLC,
no prior CT,* and tumor
tissue available for
biomarker analysis
(N = 1202)
Carboplatin/Paclitaxel†
(n = 402)
Bevacizumab + Carboplatin/Paclitaxel†§
(n = 400)
Bevacizumab + Carboplatin/Paclitaxel†
(n = 400)
Stratified by sex,
PD-L1 expression,
liver metastases
Atezolizumab
Atezolizumab +
Bevacizumab
Bevacizumab
Data cutoff: January 22, 2018.
*If sensitizing EGFR mutation or ALK translocation present, must have PD on or intolerance to ≥ 1 approved targeted therapy.
†Bevacizumab 15 mg/kg; carboplatin AUC 6; paclitaxel 200 mg/m2; all given IV Q3W for 4 or 6 cycles. ‡No crossover permitted. §Control arm.
Atezolizumab
until PD or loss
of clinical
benefit and/or
bevacizumab
until PD
Maintenance‡
Socinski MA, et al. ASCO 2018. Abstract 9002. Socinski MA, et al. N Engl J Med. 2018; 378:2288-2301.

116171
IMpower150: Updated PFS in ITT WT Population*
*ITT WT: patients without EGFR or ALK genetic alterations; 87% of randomized patients.
Atezolizumab +
Bev + Carbo/Pac
Bev + Carbo/Pac
Median PFS,
mos (95% CI)
8.3
(7.7-9.8)
6.8
(6.0-7.1)
6-mo PFS, % 66 56
12-mo PFS, % 38 20
18-mo PFS, % 27 8
Median follow-up: ~ 20 mos.
HR: 0.59 (95% CI: 0.50-0.70; P < .0001)
PFS(%)
Mos
100
90
80
70
60
50
40
30
20
10
0
340 2 3 4 5 6 7 8 9 10 1112131415 18192021222324252627282930313233
+
+
+
++ ++
+
+
+++ ++ +++++ +++++++++++
+ ++
+
+++
++++ ++ +++++ +++++
++ + ++ ++ + ++ +
+++++++ ++++ +++
+
++
++
+
+
+++
+
Socinski MA, et al. ASCO 2018. Abstract 9002.
Atezolizumab +
Bev + Carbo/Pac Bev + Carbo/Pac
Patients, n 359 337
Median OS, mos
(95% CI)
19.2
(17.0-23.8)
14.7
(13.3-16.9)
12-mo OS, % 67 61
18-mo OS, % 53 41
24-mo OS, % 43 34
34
50
OS(%)
HR: 0.78 (95% CI: 0.64-0.96; P = .0164)
Mos
100
90
80
70
60
40
30
20
10
0
330 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132
++
+
++ +
+
+
+
+
++++
+++++++ ++ +++++
+
+++
+ +++ +++
++++++++++++++++++++++++++ ++
+
++
+
+ ++ +
+++++++++++++++++++++++++++++++++++++++
+++++ ++
+++++++++ ++++++++
++++++++++
+
+
++++++ ++ +++ +
+
+++++ +++++ +
+
+
+
+++++++++++++++++
++++
+++ +
++++

IMpower150: PFS by Subgroup
Favors
Atezolizumab + Bev + Carbo/Pac
Favors
Bev + Carbo/Pac
0.25 1.00 1.25
Patients, n (%) HR (95% CI)Median PFS, MosPopulation
0.61 (0.52-0.72)
0.59 (0.37-0.94)
0.62 (0.52-0.74)
0.39 (0.25-0.60)
0.50 (0.39-0.64)
0.56 (0.41-0.77)
0.68 (0.56-0.82)
0.77 (0.61-0.99)
0.51 (0.38-0.68)
0.76 (0.60-0.96)
8.3
9.7
8.3
12.6
11.0
8.3
8.0
7.1
11.3
7.3
6.8
6.1
6.8
6.8
6.8
6.6
6.8
6.9
6.8
7.0
800 (100)
108 (14)
692 (87)
135 (20)
354 (51)
224 (32)
557 (80)
338 (49)
284 (43)
374 (57)
ITT population
Patients with EGFR or ALK
genetic alterations
WT population
PD-L1 subgroups (in WT population)*
TC3 or IC3
TC1/2/3 or IC1/2/3
TC1/2 or IC1/2
TC0/1/2 and IC0/1/2
TC0 and IC0
Teff subgroups (in WT population)
High gene signature expression
Low gene signature expression
ABCP BCP
Socinski MA, et al. N Engl J Med. 2018; 378:2288-2301.
*TC3 or IC3: PD-L1 expression ≥ 50% TCs or ≥ 10% TI immune cells; TC1/2/3 or IC1/2/3: ≥ 1% TCs
or TI immune cells; TC1/2 or IC1/2: ≥ 1% TCs or TI immune cells and < than 50% of tumor cells or
< 10% of TI immune cells; TC0/1/2 and IC0/1/2: < 50% of TCs and < 10% of TI immune cells; and
TC0 and IC0, < 1% TCs and TI immune cells.

Immunotherapy advances in lung cancer

Recomendados

Recomendados

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Semelhante a Immunotherapy advances in lung cancer

Semelhante a Immunotherapy advances in lung cancer (20)

Mais de Alok Gupta

Mais de Alok Gupta (20)

Último

Último (20)

Immunotherapy advances in lung cancer