Efficacy
The pivotal coBRIM trial – an international, multicentre study3,4
A randomised, double-blind, placebo-controlled study of COTELLIC® + ZELBORAF® vs placebo + ZELBORAF® in 495 patients with previously untreated BRAFV600 mutation-positive unresectable or metastatic melanoma

Primary endpoint |
Secondary efficacy endpoints |
Investigator-assessed progression-free survival (PFS)
|
Overall survival (OS) |
Confirmed objective response rate (ORR) |
|
Duration of response (DoR) |
|
PFS as assessed by blinded independent review |
No filter results
Patient demographics
Patient demographics and baseline characteristics were well balanced in coBRIM4
Baseline characteristics | COTELLIC + ZELBORAF (n=247) |
Placebo + ZELBORAF (n=248) |
|
Median age, years | 56 | 55 | |
Sex, no. (0/o) | Male | 146 (59) | 140 (56) |
Female | 10 1 (41 ) | 108 (44) | |
Caucasian, no. (0/o) | 227 (92) | 235 (95) | |
Geographic region, no. (0/o) | Au stralia, New Zealand, or Israel | 40 ( 16) | 38 ( 15) |
Europe | 182 (74) | 184 (74) | |
North America | 25 ( 10) | 26 ( 10) | |
ECOG performance status score,a no. (0/o) | 0 | 184 (76) | 164 (67) |
1 | 58 (24) | 80 (33) | |
2 | 1 ( < 1) | 0 (-) | |
Metastatic status, no. (0/o) | Unresectable stage 1 1 1 C | 2 1 (9) | 13 (5) |
M1a | 40 ( 16) | 40 ( 16) | |
M1b | 40 ( 16) | 42 ( 17) | |
M1c | 146 (59) | 153 (62) | |
Elevated LDHb no. (0/o) | 112 (46) | 104 (43) | |
History of brain metastases, no.(0/o) | 1 ( < 1) | 2 ( 1) | |
BRAF-mutation genotype,'no. (0/o) | V600E | 170 (69) | 174 (70) |
V600K | 24 ( 10) | 32 ( 13) | |
Not eva lua ble | 53 (21 ) | 42 ( 17) |
No filter results
aECOG performance status analyses: n=243 for COTELLIC® + ZELBORAF® and n=244 for placebo + ZELBORAF®.
bElevated LDH analyses: n=242 for COTELLIC® + ZELBORAF® and n=242 for placebo + ZELBORAF®.
cAll patients were BRAFV600 mutation positive according to the Cobas® 4800 BRAF V600 Mutation Test. After randomisation, next-generation sequencing was used to further classify mutations as V600E or V600K. Cases that could not be evaluated were those in which either no tumour sample was provided or sequencing could not be performed on the tissue provided.
ECOG=Eastern Cooperative Oncology Group; LDH=lactate dehydrogenase
Survival data
Primary endpoint: Significant improvement in investigator-assessed PFS1,3

CI=confidence interval; HR=hazard ratio; PFS = progression-fress survival
- 42% reduced risk of disease progression or death: Median PFS of 12.3 months (95% CI, 9.5–13.4 months) with COTELLIC® + ZELBORAF® vs 7.2 months (95% CI, 5.6–7.5 months) with placebo + ZELBORAF (HR=0.58; 95% CI, 0.46–0.72; P<0.0001)
- 143 (58%) events with COTELLIC® + ZELBORAF® vs 180 (73%) events with placebo + ZELBORAF®
PFS results were consistent as confirmed by blinded independent review4
- 11.3 months median PFS as assessed by blinded independent review with COTELLIC® + ZELBORAF® vs 6.0 months with placebo + ZELBORAF® (95% CI, 8.5 months–not reached [NR] vs 5.6–7.5 months), a 5.3-month improvement in median PFS (HR=0.60; 95% CI, 0.45–0.79; P=0.0003)
- 82 (33%) events with COTELLIC® + ZELBORAF® vs 117 (47%) with placebo + ZELBORAF®
Secondary endpoint: Significant improvement in OS1,3

CI=confidence interval; HR=hazard ratio; OS = overall survival
- 30% reduction in risk of death: Median OS 22.3 months with COTELLIC® + ZELBORAF® vs 17.4 months with placebo + ZELBORAF® (95% CI, 20.3 months–not estimable vs 15.0–19.8 months) (HR=0.70; 95% CI, 0.55–0.90; P=0.005)
- 114 (46%) deaths and 141 (57%) deaths in the COTELLIC® + ZELBORAF® and placebo + ZELBORAF® arms, respectively
Significant improvement in ORR3

CI = confidence interval; ORR = objective response rate
- In both study arms, the majority of patients responded to treatment within 8 weeks, the time of the first tumour assessment*4
*Exploratory analysis of the coBRIM trial.
Achieve durable responses with COTELLIC® + ZELBORAF®3,4
Median DoR: 13.0 months with COTELLIC® + ZELBORAF® vs 9.2 months with placebo + ZELBORAF® (95% CI, 11.1–16.6 months vs 7.5–12.8 months)