NSCLC: KEYNOTE-189 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

PEMB+peme/pct

PLB+peme/pct

410

206

Phase:

3

Randomisation:

Double blind

Primary tumour:

NSCLC

Subtype (biomarker):

Nonsquamous

Stage:

meta

Line of therapy:

L1

Primary
PEMB+peme/pct
PLB+peme/pct
HR
p
OS @1yr
69.2%
49.4%
0.49 (0.38-0.64)
<0.001
PFS
8.8 mo
4.9 mo
0.52 (0.43-0.64)
<0.001
Secondaries
PEMB+peme/pct
PLB+peme/pct
HR
p
ORR
47.6%
18.9%
CR
0.5%
0.5%
Time to response
2.2 mo
1.4 mo
DoR
11.2 mo
7.8 mo
(all grades, %)
PEMB+peme/pct
PLB+peme/pct
p
Any AE gr.≥3
67.2%
65.8%
NA
AE leading to discontinuation of any treatment component
27.7
14.9
NA
AE leading to death
6.7
5.9
NA
Nausea
55.6
52.0
NA
Anemia
46.2
46.5
NA
Diarrhea
30.9
21.3
NA
Neutropenia
27.2
24.3
NA
Thrombocytopenia
18.0
14.4
NA
Hypothyroidism
6.7
2.5
NA
Hyperthyroidism
4.0
3.0
NA
Pneumonitis
4.4
2.8
NA
Colitis
3.1
0.0
NA
Nephritis
2.4
0.0
NA
Hepatitis
1.7
0.0
NA
  • Inclusion
  • Exclusion

- Has a histologically-confirmed or cytologically confirmed diagnosis of stage IV nonsquamous NSCLC. - Has confirmation that epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)-directed therapy is not indicated. - Has measurable disease. - Has not received prior systemic treatment for their advanced/metastatic NSCLC. - Can provide tumor tissue. - Has a life expectancy of at least 3 months. - Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status. - Has adequate organ function - If female of childbearing potential, is willing to use adequate contraception for the course of the study through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents. - If male with a female partner(s) of child-bearing potential, must agree to use adequate contraception starting with the first dose of study medication through 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.

- Has predominantly squamous cell histology NSCLC. - Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab. - Before the first dose of study medication: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease, b) Has received antineoplastic biological therapy (e.g., erlotinib, crizotinib, cetuximab), c) Had major surgery (<3 weeks prior to first dose) - Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study medication. - Completed palliative radiotherapy within 7 days of the first dose of study medication. - Is expected to require any other form of antineoplastic therapy while on study. - Received a live-virus vaccination within 30 days of planned start of study medication. - Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis. - Known history of prior malignancy except if participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy, except for successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb). - Known sensitivity to any component of cisplatin, carboplatin or pemetrexed. - Has active autoimmune disease that has required systemic treatment in past 2 years. - Is on chronic systemic steroids. - Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam). - Is unable or unwilling to take folic acid or vitamin B12 supplementation. - Had prior treatment with any other anti-programmed cell death-1 (PD-1), or PD-ligand 1 (PD-L1) or PD-L2 agent or an antibody targeting other immuno-regulatory receptors or mechanisms. Has participated in any other pembrolizumab study and has been treated with pembrolizumab. - Has an active infection requiring therapy. - Has known history of Human Immunodeficiency Virus (HIV). - Has known active Hepatitis B or C. - Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. -Is a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol). - Has symptomatic ascites or pleural effusion. - Has interstitial lung disease or a history of pneumonitis that required oral of IV glucocorticoids to assist with management. -Is pregnant or breastfeeding, or expecting to conceive or father children prior to 120 days after the last dose of study medication or through 180 days after last dose of chemotherapeutic agents.

Characteristics
PEMB+peme/pct
PLB+peme/pct
Agedc-comma sex - no.(%)
Median age (range) yr
65 (34–84)
63.5 (34–84)
<65 yr
197 (48.0)
115 (55.8)
Male
254 (62.0)
109 (52.9)
Region of enrollment - no.(%)
Europe
243 (59.3)
131 (63.6)
North America
111 (27.1)
46 (22.3)
East Asia
4 (1.0)
6 (2.9)
Other region
52 (12.7)
23 (11.2)
ECOG PS score - no.(%)
0
186 (45.4)
80 (38.8)
1
221 (53.9)
125 (60.7)
2
1 (0.2)
0
Smoking status - no.(%)
Current or former
362 (88.3)
181 (87.9)
Never
48 (11.7)
25 (12.1)
Histologic features - no.(%)
Adenocarcinoma
394 (96.1)
198 (96.1)
NSCLC not otherwise specified
10 (2.4)
4 (1.9)
Other
6 (1.5)
4 (1.9)
Brain metastases - no.(%)
73 (17.8)
35 (17.0)
PD-L1 tumor proportion score - no.(%)
<1%
127 (31.0)
63 (30.6)
≥1%
260 (63.4)
128 (62.1)
1-49%
128 (31.2)
58 (28.2)
≥50%
132 (32.2)
70 (34.0)
Previous therapy for nonmetastatic disease - no.(%)
Thoracic radiotherapy
28 (6.8)
20 (9.7)
Neoadjuvant therapy
5 (1.2)
6 (2.9)
Adjuvant therapy
25 (6.1)
14 (6.8)
Ad-hoc:
no.pts inv.
no.pts comp.
PEMB+peme/pct
PLB+peme/pct
HR
p
ORR (PD-L1<1%)
127
63
32.3%
14.3%
ORR (PD-L1 1-49%)
128
58
48.4%
20.7%
ORR (PD-L1≥50%)
132
70
61.4%
22.9%
  • OS @1yr
  • PFS
analisys of OS @1yr
PEMB+peme/pct
PLB+peme/pct
HR (95% CI)
Age
<65 yr (n=312)
0.43 (0.31–0.61)
≥65 yr (n=304)
0.64 (0.43–0.95)
Sex
Male (n=363)
0.70 (0.50–0.99)
Female (n=253)
0.29 (0.19–0.44)
ECOG
0 (n=266)
0.44 (0.28–0.71)
1 (n=346)
0.53 (0.39–0.73)
Smoking status
Current of former (n=543)
0.54 (0.41–0.71)
Never (n=73)
0.23 (0.10–0.54)
Brain metastases at baseline
Yes (n=108)
0.36 (0.20–0.62)
No (n=508)
0.53 (0.39–0.71)
PD-L1 tumor proportion score
<1% (n=190)
61.7%
52.2%
0.59 (0.38–0.92)
≥1% (n=388)
0.47 (0.34–0.66)
PD-L1 tumor proportion score
1-49% (n=186)
71.5%
50.9%
0.55 (0.34–0.90)
≥50% (n=202)
73.0%
48.1%
0.42 (0.26–0.68)
Platinum-based drug
Carboplatin (n=445)
0.52 (0.39–0.71)
Cisplatin (n=171)
0.41 (0.24–0.69)
analisys of PFS
PEMB+peme/pct
PLB+peme/pct
HR (95% CI)
Age
< 65 yr (n=312)
0.43 (0.32–0.56)
≥ 65 yr (n=304)
0.75 (0.55–1.02)
Sex
Male (n=363)
0.66 (0.50–0.87)
Female (n=253)
0.40 (0.29–0.54)
ECOG
0 (n=266)
0.49 (0.35–0.68)
1 (n=346)
0.56 (0.43–0.72)
Smoking status
Current or former (n=543)
0.54 (0.43–0.66)
Never (n=73)
0.43 (0.23–0.81)
Brain metastases at baseline
Yes (n=108)
0.42 (0.26–0.68)
No (n=508)
0.53 (0.43–0.67)
PD-L1 tumor proportion score
< 1% (n=190)
0.75 (0.53–1.05)
≥ 1% (n=388)
0.44 (0.34–0.57)
PD-L1 tumor proportion score
1-49% (n=186)
0.55 (0.37–0.81)
≥ 50% (n=202)
0.36 (0.25–0.52)
Platinum-based drug
Carboplatin (n=445)
0.55 (0.44–0.70)
Cisplatin (n=171)
0.44 (0.30–0.65)