off date: 19 May 2016
PFS (primary analysis)
Number of events (progressive disease(PD)) (%)
98 (51.0)
96 (49.5)
106 (55.5)
Median, months
(95 % CI)
14.9
(11.0, 18.5)
9.6
(7.5, 14.8)
7.3
(5.6, 8.2)
HRa (95 % CI) (vs Vem)
p value (stratified log-rank)b
0.54 (0.41, 0.71)
< 0.001
HRa (95 % CI) (vs. Vem)
Nominal p-value
0.68 (0.52, 0.90)
0.007
HRa (95 % CI) (vs Enco 300)
p value (stratified log-rank)b
0.75 (0.56, 1.00)
0.051
Confirmed overall responses
Overall response rate, n (%)
(95 % CI)
121 (63.0)
(55.8, 69.9)
98 (50.5)
(43.3, 57.8)
77 (40.3)
(33.3, 47.6)
CR, n (%)
15 (7.8)
10 (5.2)
11 (5.8)
PR, n (%)
106 (55.2)
88(45.4)
66 (34.6)
SD, n (%)
46 (24.0)
53(27.3)
73 (38.2)
DCR, n (%)
(95 % CI)
177 (92.2)
(87.4, 95.6)
163 (84.0)
(78.1, 88.9)
156 (81.7)
(75.4, 86.9)
Duration of response
Median, months
(95 % CI)
16.6
(12.2, 20.4)
14.9
(11.1, NE)
12.3
(6.9, 16.9)
Updated analysis, cut-off date: 07 November 2017
PFS
Number of events (progressive disease) (%)
113 (58.9)
112 (57.7)
118 (61.8)
Median, months
(95% CI)
14.9
(11.0, 20.2)
9.6
(7.4,14.8)
7.3
(5.6, 7.9)
HRa (95% CI) (vs Vem)
Nominal p-value
0.51 (0.39, 0.67)
<0.001
HRa (95% CI) (vs Vem)
Nominal p-value
0.68 (0.52, 0.88)
0.0038
HRa (95% CI) (vs Enco 300)
Nominal p-value
0.77 (0.59,1.00)
0.0498
CI = confidence interval; CR = complete response; DCR = disease control rate (CR+PR+SD+Non- CR/Non-PD; Non-CR/Non-PD applies only to patients without a target lesion who did not achieve CR or have PD); HR = hazard ratio; NE = not estimable; PFS = progression-free survival; PR = partial response; SD = stable disease. Vem = vemurafenib.
a Hazard ratio based on a stratified Cox proportional hazard model
b Log-rank p-value (2-sided)
Figure 1: Study CMEK162B2301, Part 1: Kaplan-Meier plot of progression-free survival by independent central review (cut-off date 19 May 2016)
An interim OS analysis of study CMEK162B2301 Part 1, (cut-off date 07 November 2017) demonstrated a statistically significant improvement in OS for Combo 450 compared with vemurafenib (see Table 5 and Figure 2).
A similar proportion of patients in each treatment arm received subsequent treatment with checkpoint inhibitors, mainly pembrolizumab, nivolumab and ipilimumab (34.4 % Combo 450 arm, 36.1 % encorafenib arm, 39.8 % vemurafenib arm).
Table 5: Study CMEK162B2301, Part 1: Overall survival interim results (cut-off date: 7 November 2017)
Encorafenib + binimetinib
n = 192
(Combo 450)
Encorafenib
n = 194
(Enco 300)
Vemurafenib
n = 191
(Vem)
OS
Number of Events (%)
105 (54.7)
106 (54.6)
127 (66.5)
Median, months
(95 % CI)
33.6
(24.4, 39.2)
23.5
(19.6, 33.6)
16.9
(14.0, 24.5)
Survival at 12 months
(95% CI)
75.5%
(68.8, 81.0)
74.6%
(67.6, 80.3)
63.1%
(55.7, 69.6)
Survival at 24 months
(95% CI)
57.6%
(50.3, 64.3)
49.1%
(41.5, 56.2)
43.2%
