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

efficiacy-study.png

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

efficiacy-survival1.png

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

efficiacy-survival2.png

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

efficiacy-survival3.png

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)