NSCLC: KEYNOTE-407 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

PEMB+carb/pacl

PLB+carb/pacl

278

281

Phase:

3

Randomisation:

Double blind

Primary tumour:

NSCLC

Subtype (biomarker):

Squamous

Stage:

meta

Line of therapy:

L1

Primary
PEMB+carb/pacl
PLB+carb/pacl
HR
p
OS
15.9 mo
11.3 mo
0.64 (0.49-0.85)
<0.001
PFS
6.4 mo
4.8 mo
0.56 (0.45-0.70)
<0.001
Secondaries
PEMB+carb/pacl
PLB+carb/pacl
HR
p
ORR
57.9%
38.4%
Time to response
1.4 mo
1.4 mo
DoR
7.7 mo
4.8 mo
CR
1.4%
2.1%
(all grades, %)
PEMB+carb/pacl
PLB+carb/pacl
p
Any AE grade 3-4
69.8
68.2
NA
Treatment-discontinuation due to AE
13.3
6.4
NA
AE leading to death
8.3
6.4
NA
Anemia
53.2
51.8
NA
Neutropenia
37.8
32.9
NA
Nausea
35.6
32.1
NA
Thrombocytopenia
30.6
23.2
NA
Diarrhea
29.9
23.2
NA
Peripheral neuropathy
20.5
16.1
NA
Vomiting
16.2
11.8
NA
Alopecia
46.0
36.4
NA
Constipation
23.0
21.8
NA
Arthralgia
20.5
14.3
NA
Dyspnea
12.9
16.1
NA
  • Inclusion
  • Exclusion

- Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer [AJCC] 7th edition) squamous NSCLC. - Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment. - Has not received prior systemic treatment for metastatic NSCLC. - Has provided tumor tissue from locations not radiated prior to biopsy. - 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 an adequate method of contraception for the course of the study through 180 days after the last dose of study drug. - If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study drug through 95 days after the last dose of study drug. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

- Has non-squamous 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 drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (<3 weeks prior to first dose). - Received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study drug. - Completed palliative radiotherapy within 7 days of the first dose of study drug. - Is expected to require any other form of antineoplastic therapy while on study. - Has received a live-virus vaccination within 30 days of planned treatment start. - Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) version 4 criteria. - Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody. - Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel. - Has active autoimmune disease that has required systemic treatment in past 2 years. - Is on chronic systemic steroids. - Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms. - Has participated in any other pembrolizumab trial 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. Active Hepatitis B. - Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol). - Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

Characteristics
PEMB+carb/pacl
PLB+carb/pacl
Agedc-comma sex
Median age (range) yr
65 (29–87)
65 (36–88)
<65 yr - no.(%)
127 (45.7)
127 (45.2)
Male - no.(%)
220 (79.1)
235 (83.6)
Region of enrollment - no.(%)
East Asia
54 (19.4)
52 (18.5)
Rest of the world
224 (80.6)
229 (81.5)
ECOG PS score - no.(%)
0
73 (26.3)
90 (32.0)
1
205 (73.7)
191 (68.0)
Smoking status - no.(%)
Current or former
256 (92.1)
262 (93.2)
Never
22 (7.9)
19 (6.8)
Histologic features - no.(%)
Squamous
272 (97.8)
274 (97.5)
Adenosquamous
6 (2.2)
7 (2.5)
Brain metastases
20 (7.2)
24 (8.5)
PD-L1 tumor proportion score - no.(%)
<1%
95 (34.2)
99 (35.2)
≥1%
176 (63.3)
177 (63.0)
1-49%
103 (37.1)
104 (37.0)
≥50%
73 (26.3)
73 (26.0)
Previous therapy for nonmetastatic disease - no.(%)
Thoracic radiotherapy
17 (6.1)
22 (7.8)
Neoadjuvant or adjuvant therapy
5 (1.8)
8 (2.8)
Ad-hoc:
no.pts inv.
no.pts comp.
PEMB+carb/pacl
PLB+carb/pacl
HR
p
ORR (PD-L1<1%)
95
99
63.2%
40.4%
ORR (PD-L1 1-49%)
103
104
49.5%
41.3%
ORR (PD-L1≥50%)
73
73
60.3%
32.9%
  • OS
  • PFS
analisys of OS
PEMB+carb/pacl
PLB+carb/pacl
HR (95% CI)
Age
<65 yr (n=254)
0.52 (0.34–0.80)
≥65 yr (n=305)
0.74 (0.51–1.07)
Sex
Male (n=455)
0.69 (0.51–0.94)
Female (n=104)
0.42 (0.22–0.81)
ECOG
0 (n=163)
0.54 (0.29–0.98)
1 (n=396)
0.66 (0.48–0.90)
PD-L1 score
<1% (n=194)
15.9 mo
10.2 mo
0.61 (0.38–0.98)
≥1% (n=353)
0.65 (0.45–0.92)
PD-L1 score
1-49% (n=207)
14.0 mo
11.6 mo
0.57 (0.36–0.90)
≥50% (n=146)
NR
NR
0.64 (0.37–1.10)
Taxane-based drug
Paclitaxel (n=336)
0.67 (0.48–0.93)
Nab-paclitaxel (n=223)
0.59 (0.36–0.98)
Region of enrollment
East Asia (n=106)
0.44 (0.22–0.89)
Rest of the world (n=453)
0.69 (0.51–0.93)
analisys of PFS
PEMB+carb/pacl
PLB+carb/pacl
HR (95% CI)
Age
<65 yr (254)
0.50 (0.37–0.69)
≥65 yr (305)
0.63 (0.47–0.84)
Sex
Male (455)
0.58 (0.46–0.73)
Female (104)
0.49 (0.30–0.81)
ECOG
0 (163)
0.45 (0.29–0.68)
1 (396)
0.61 (0.48–0.78)
PD-L1 score
<1% (194)
0.68 (0.47–0.98)
≥1% (353)
0.49 (0.38–0.65)
PD-L1 score
1-49% (207)
0.56 (0.39–0.80)
≥50% (146)
0.37 (0.24–0.58
Taxane-based drug
Paclitaxel (336)
0.52 (0.40–0.68)
Nab-paclitaxel (223)
0.65 (0.45–0.94)
Region of enrollment
East Asia (106)
0.49 (0.30–0.82)
Rest of the world (453)
0.58 (0.46–0.73)