Investor science conference call from - ESMO 2012 Vienna, 2 October 2012 - Roche
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Investor science conference call from ESMO 2012 Vienna, 2 October 2012
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2
Introduction Dr. Karl Mahler, Head of Investor Relations, Roche
Investor events 2012
R&D and strategy updates
Date /
location Event Key assets / newsflow
4 June 2012 ASCO (American Society of Clinical T-DM1: EMILIA pretreated HER2+ mBC
Chicago, USA Oncology) Avastin: TML treatment through multiple
lines in mCRC, AURELIA platinum resistant
ovarian cancer
8 June 2012 EULAR (Annual European Congress of Actemra: ADACTA RA monotherapy head to
Berlin, Germany Rheumatology ) head versus adalimumab
4/5 September 2012 Investor Day R&D strategy and pipeline
London, GB Growth opportunities
Innovation and efficiency
2 October 2012 ESMO (European Society for Medical Herceptin: HERA HER2+ early BC final
Vienna, Austria Oncology) analysis; T-DM1: EMILIA pretreated HER2+
mBC updated OS data; Zelboraf early data
from MEK combo and brain mets study
4
Oncology represents 60% of new molecules in
R&D pipeline
Phase I Phase II Phase III
(38 NMEs) (23 NMEs) (9 NMEs)
MDM2 ant solid & hem tumors Bcl-2 inh CLL and NHL EGFR MAb solid tumors T-DM1 HER2+ mBC
HER3 MAb solid tumors ChK1 inh solid tum & lymphoma PI3K inh solid tumors onartuzumab (MetMAb) solid tumors
CSF-1R MAb solid tumors PI3K inh solid tumors PI3K/mTOR inh solid & hem tumors obinutuzumab (GA101) hem. tumors
CIF/MEK inh solid tumors ADC metastatic melanoma EGFL7 MAb solid tumors lebrikizumab severe asthma
Tweak MAb oncology PI3k inh glioblastoma 2L HER3/EGFR m. epithelial tumors aleglitazar CV risk reduction in T2D
BRAF inh (2) BRAF mut melanoma ChK1 inh(2) solid tumors glypican-3 MAb liver cancer tofogliflozin (SGLT2) type 2 diabetes
Raf & MEK dual inh solid tumors ALK inhibitor NSCLC etrolizumab ulcerative colitis ocrelizumab MS
CD44 MAb solid tumors PI3K inh solid tumors rontalizumab SLE bitopertin schizophrenia
MEK inh solid tumors WT-1 peptide cancer vaccine LT alpha MAb RA arbaclofen fragile X syndrome (FXS)
MEK inh solid tumors IL-17 MAb autoimmune diseases M1 prime MAb asthma
MDM2 ant solid & hem tumors IL-6 MAb RA mericitabine HCV
AKT inhibitor solid tumors TLR7 agonist HBV danoprevir HCV Registration
PD-L1 MAb solid tumors - infectious diseases setrobuvir HCV (2 NMEs)
Steap 1ADC prostate ca. GIP/GLP-1 dual ago type 2 diabetes 11 beta HSD inh metabolic diseases
ADC ovarian ca. GABRA5 NAM cogn. disorders P selectin MAb ACS/CVD Perjeta (pertuzumab)* HER2+ mBC 1L
CD22 ADC hem malignancies V1 receptor antag autism oxLDL MAb sec prev CV events Erivedge* advanced BCC
anti-angiogenic solid tumors BACE inh Alzheimer’s PCSK9 MAb metabolic diseases
ADC heme tumors gantenerumab Alzheimer’s
ADC multiple myeloma MAO-B inh Alzheimer’s
ADC oncology mGluR2 antag depression
ADC oncology mGluR5 antag TRD
crenezumab Alzheimer‘s
anti-factor D Fab geograph. atrophy
Oncology CardioMetabolism
Immunology Neuroscience
Virology Ophthalmology
As of June 30 2012; * Approved in US, filed in EU
5
Herceptin to prevent breast cancer recurrences in 28,000 women Over 10 years in 5 major EU countries alone No. of women expected to be prevented from breast cancer recurrence Incidence of HER2-positive mBC without Herceptin Reference: Weisgerber-Kriegl, U. et al. 2008. J Clin Oncol; ASCO Annual Meeting Proceedings: 26:15S 6
Agenda
Introduction
Dr. Karl Mahler, Head of Investor Relations
Update on HER2 breast cancer and skin cancer franchises
Stefan Frings MD, Global Head Medical Affairs Oncology, Roche
T-DM1: Updated overall survival results from EMILIA
Herceptin optimal duration of treatment in early breast cancer
• Final analysis of HERA: 2 years versus 1 year of trastuzumab after adjuvant
chemotherapy
• PHARE: 6 months versus 1 year of trastuzumab in adjuvant early breast cancer
Metastatic melanoma
• BRIM7 phase Ib data of Zelboraf in combination with MEK inhibitor RG7421
• Phase I Zelboraf single-arm study in patients with brain metastases
7
Stefan Frings MD, Global Head Medical Affairs Oncology, Roche
Redefine the standard of care
Reshape the biologics market for HER2-positive
breast cancer
2nd line Xeloda + T-DM1 (EMILIA)
mBC lapatinib
1st line Herceptin Herceptin & Perjeta +
T-DM1 & Perjeta (MARIANNE)
mBC + chemo chemo (CLEOPATRA)
Adjuvant Herceptin Herceptin subcutaneous + chemo Herceptin & Perjeta T-DM1 & Perjeta
BC + chemo (HannaH) + chemo (APHINITY) + chemo
2011 2012 2013 2014 2015 2016 2017 2018 2019 2020
Filing timelines
Established standard of care Potential new standard of care Potential future standard of care
9Updated Overall Survival Results From EMILIA,
a Phase 3 Study of Trastuzumab Emtansine (T-DM1)
vs Capecitabine and Lapatinib in HER2-Positive
Locally Advanced or Metastatic Breast Cancer
S Verma,1 D Miles,2 L Gianni,3 IE Krop,4 M Welslau,5
J Baselga,6 M Pegram,7 D-Y Oh,8 V Diéras,9 E
Guardino,10 L Fang,10 MW Lu,10 S Olsen,10 K Blackwell11
1Sunnybrook Odette Cancer Center, Toronto, Canada; 2Mount Vernon Cancer
Center, Northwood, UK; 3San Raffaele Hospital, Milan, Italy; 4Dana-Farber Cancer
Institute, Boston, MA, USA; 5Medical Office Hematology, Aschaffenburg, Germany;
6Massachusetts General Hospital, Boston, MA, USA; 7University of Miami Sylvester
Comprehensive Cancer Center, Miami, FL, USA; 8Seoul National University College
of Medicine, Seoul, Korea; 9Institut Curie, Paris, France; 10Genentech, Inc, South
San Francisco, CA, USA; 11Duke Cancer Institute, Durham, NC, USA
10
www.esmo2012.org 10EMILIA Study Design
HER2-positive LABC
or MBC (N=980) T-DM1
PD
3.6 mg/kg q3w IV
• Prior taxane and
trastuzumab 1:1
• Progression on Capecitabine
metastatic treatment 1000 mg/m2 PO bid, days 1–14, q3w
or within 6 months of + PD
adjuvant treatment Lapatinib
1250 mg/day PO qd
• Stratification factors: World region, number of prior chemo regimens for MBC or
unresectable LABC, presence of visceral disease
• Primary endpoints: PFS by independent review, OS, and safety
• Key secondary endpoints: PFS by investigator, ORR, DOR
• Statistical considerations: Hierarchical statistical analysis was performed in pre-specified
sequential order: PFS by independent review → OS → secondary endpoints
PFS analysis: 90% power to detect HR=0.75; 2-sided alpha 5%
OS analyses: 80% power to detect HR=0.80; 2-sided alpha 5% 11
www.esmo2012.org 11Progression-Free Survival
by Independent Review
1.0 Median No. of
(months) events
Cap + Lap 6.4 304
Proportion progression-free
0.8 T-DM1 9.6 265
Stratified HR=0.650 (95% CI, 0.55, 0.77)
POverall Survival: First Interim Analysis
Median (months) No. of events
Cap + Lap 23.3 129
T-DM1 NR 94
1.0 Stratified HR=0.621 (95% CI, 0.48, 0.81); P=0.0005
84.7% Efficacy stopping boundary P=0.0003 or HR=0.617
0.8
Proportion surviving
77.0% 65.4%
0.6
47.5%
0.4
0.2
0.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
No. at risk: Time (months)
Cap + Lap 496 469 438 364 296 242 195 155 129 97 74 52 31 17 7 3 2 1 0
T-DM1 495 484 461 390 331 277 220 182 149 123 96 67 46 29 16 5 2 0 0
Unstratified HR=0.63 (P=0.0005).
NR, not reached. 13
www.esmo2012.org 13Overall Survival: Second Interim Analysis
(confirmatory analysis)
Median (months) No. of events
Cap + Lap 25.1 182
T-DM1 30.9 149
1.0 Stratified HR=0.682 (95% CI, 0.55, 0.85); P=0.0006
85.2% Efficacy stopping boundary P=0.0037 or HR=0.727
0.8
Proportion surviving
78.4%
64.7%
0.6
51.8%
0.4
0.2
0.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
No. at risk: Time (months)
Cap + Lap 496 471 453 435 403 368 297 240 204 159 133 110 86 63 45 27 17 7 4
T-DM1 495 485 474 457 439 418 349 293 242 197 164 136 111 86 62 38 28 13 5
Data cut-off July 31, 2012; Unstratified HR=0.70 (P=0.0012). 14
www.esmo2012.org 14Conclusions
In the EMILIA study, T-DM1 achieved:
• Significant improvement in PFS
– Median PFS: Cap + Lap 6.4 mos; T-DM1 9.6 mos
– HR=0.650; PHerceptin in adjuvant HER2-positive breast cancer
Herceptin 1 year is the regulatory and clinical
standard endorsed by guidelines for early BC
Herceptin optimal duration of use in adjuvant setting
1 year of treatment SOC
Shorter duration trials • Based on 4 large phase Longer duration trial
III studies*
PHARE, PERSEPHONE • Adjuvant setting HERA
and others approved in 2006
• 6 months vs. 1 year • Overall, more than 1.2 • 2 years vs. 1 year
million patients treated
*HERA, NCCTG N9831, NSABP B-31, BCIRG006
17HERA TRIAL: 2 years versus 1 year of
trastuzumab after adjuvant chemotherapy
in women with HER2-positive early breast
cancer at 8 years of median follow up
Aron Goldhirsch, Martine J. Piccart-Gebhart, Marion Procter,
Evandro de Azambuja, Harald A. Weber, Michael Untch, Ian Smith, Luca Gianni,
Christian Jackisch, David Cameron, Richard Bell, Mitch Dowsett, Richard D. Gelber,
Brian Leyland-Jones, and José Baselga on behalf of the HERA Study Team
ESMO Congress, Vienna – 1 October 2012HERA TRIAL DESIGN
2001 – 2005 (n=5102)
Women with locally determined HER2-
positive invasive early breast cancer
Surgery + (neo)adjuvant CT ± RT
Centrally confirmed IHC 3+ or FISH+
and LVEF ≥ 55%
Randomization
OBSERVATION 1 year Trastuzumab 2 years Trastuzumab
n=1698 8 mg/kg – 6 mg/kg 8 mg/kg – 6 mg/kg
3 weekly schedule 3 weekly schedule
n=1703 n=1701
After ASCO 2005,
option of switch
to Trastuzumab
CT, chemotherapy; RT, radiotherapy 19DFS FOR 2 YEARS VS. 1 YEAR
TRASTUZUMAB AT 8 YRS MFU
100 89.1%
81.6%
Disease-free survival (%)
80 86.7% 75.8%
81.0%
76.0%
60
Trastuzumab 2 years
Trastuzumab 1 year
40
Pts Events HR (2 vs 1) 95% CI p-value
20 2 years 1553 367 0.99 (0.85-1.14) 0.86
1 year 1552 367
0
0 1 2 3 4 5 6 7 8 9
Years from randomization
No. at risk
Trastuzumab 2 years 1553 1553 1442 1361 1292 1223 1153 1051 633 194
Trastuzumab 1 year 1552 1552 1413 1319 1265 1214 1180 1071 649 205
20confidential
SUMMARY: ANALYSIS OF 2 YEARS
VS. 1 YEAR TRASTUZUMAB
• No evidence of long-term benefit of 2 years compared to
1 year trastuzumab when administered as sequential
treatment following chemotherapy.
• Short term DFS gain for the 2 years arm in the hormone
receptor negative cohort raises hypotheses, and
illustrates need to evaluate results by receptor status.
• Secondary cardiac endpoints and other adverse events
are increased in the 2 years trastuzumab arm.
21SUMMARY OF DFS AND OS ANALYSES FOR confidential
1 YEAR TRASTUZUMAB VS. OBSERVATION
ACROSS ANALYSIS TIME POINTS
Median follow-up No. of DFS events
(% follow-up time after DFS benefit 1 year trastuzumab
selective crossover) vs observation
2005 0.54 127 vs 220
1 yr MFU
(0%) PSUMMARY: ANALYSIS OF DFS AND OS confidential
FOR 1 YEAR TRASTUZUMAB VS.
OBSERVATION AT 8 YRS MFU
• HERA results at 8 yrs MFU show sustained and
statistically significant DFS and OS benefit for 1 year
trastuzumab versus observation in ITT analyses despite
selective crossover.
• 1 year of trastuzumab remains the standard of care as
part of an adjuvant therapy for patients with HER2-
positive early breast cancer.
23Protocol of
Herceptin®
Adjuvant with
Reduced
Exposure
PHARE* Trial results comparing
6 to 12 months of trastuzumab in
adjuvant early breast cancer
Xavier Pivot, Gilles Romieu, Hervé Bonnefoi, Jean-Yves Pierga, Pierre
Kerbrat, Thomas Bachelot, Alain Lortholary, Marc Espié, Pierre Fumoleau,
Daniel Serin, Jean-Philippe Jacquin, Christelle Jouannaud, Maria Rios,
Sophie Abadie-Lacourtoisie, Nicole Tubiana-Mathieu, Laurent Cany,
Stéphanie Catala, David Khayat, Iris Pauporté, Andrew Kramar.
*lighthouse in French
www.esmo2012.orgStudy design
trastuzumab up to 12 months
trastuzumab 6 months
R
Stratification
1. ER pos / neg
2. Chemo: conco/ seq stop trastuzumab
Clinical exam
LVEF …
0 3 6 9 12 15 18 21 24 30 mos
Mammography Up to 60 mos…
R: Randomization after informed consent
www.esmo2012.org
25Statistical Methods
• Non inferiority randomized trial
– 2% variation in terms of absolute difference of recurrence
– The 95% CI HR margins should not cross the 1.15 boundary
– 1040 DFS events required for 80% power at 5% level
or
4 years of accrual and at least 2 years of follow-up
– HR were estimated from the stratified Cox model
• Accrual target: 3400 patients
www.esmo2012.org
26Study information
Activated: 30/05/2006
Randomization
3384 patients
4 patients excluded from analysis
1 Informed consent not signed
1 Randomized twice
2 HER2 negative after FISH testing
Trastuzumab 12 months Trastuzumab 6 months
1690 patients 1690 patients
•May 28th 2010 – IDMC meeting
“After careful thought and lengthy debate we recommend that entry to the trial be suspended.
We do not recommend, at this time, a crossover to a longer duration of intervention for the 6
month group but would reserve the option of such a recommendation for the future, dependent on
how the data develop”
Closed: 09/07/2010
Database locked: 31/07/2012 www.esmo2012.org
27Disease Free Survival
97.0 93.8 90.7 87.8
1.00
0.75 95.5 91.2 87.8 84.9
Probability
0.50
Events HR 95%CI p-value
0.25 H 12m 176
H 6m 219 1.28 (1.05 – 1.56) 0.29
0.00
0 12 24 36 48 60
Months
At risk
H-12m 1690 1613 1390 980 544 18
H 6m 1690 1586 1353 939 526 23
H-12m H-6m
www.esmo2012.org
28
* Cox model stratified by ER status and concomitant chemotherapyDFS Forest plot
Age yrs
60 (1128) 1.08 (0.75 - 1.54)
Nodal status
Negative (1842) 1.31 (0.93 - 1.84)
1-3 pos. nodes (1008) 1.27 (0.90 - 1.78)
>3 pos. nodes (497) 1.22 (0.85 - 1.75)
Tumour size (cm)
0-2 (1771) 1.00 (0.71 - 1.42)
2-5 (1294) 1.46 (1.09 - 1.95)
>5 (242) 1.23 (0.75 - 2.00)
Estrogene Receptor
Negative (1412) 1.32 (1.01 - 1.74)
Positive (1968) 1.23 (0.92 - 1.65)
Chemotherapy
Sequential (1428) 1.39 (1.05 - 1.85)
Concomitant (1952) 1.17 (0.89 - 1.54)
All patients (3380) 1.28 (1.05 - 1.56)
0 .5 1 1.15 1.5 2 2.5
HR
Favors 6mo Favors 12mo
www.esmo2012.org
29Overall Survival
42.5mos. median FU
99.9 98.7 96.9 95.0
1.00
99.3 97.2 95.2 93.1
0.75
Probability
0.50
Events HR 95%CI p-value
0.25 H 12m 66
H 6m 93 1.47 (1.07 – 2.02)
0.00
0 12 24 36 48 60
Months
At risk
H-12m 1690 1662 1463 1042 583 19
H 6m 1690 1645 1438 1016 566 25
H-12m H-6m
www.esmo2012.org
30
* Cox model stratified by ER status and concomitant chemotherapySummary Discussant Sandra Swain, MD
Noninferiority Trials
• Null Hypothesis: Treatments differ by more than an
acceptable level, Δ
• Alternate Hypothesis: Treatments do not differ more
than Δ
• PHARE: Δ is 15% increase in DFS HR or HR of 1.15
• Hoping to reject the null and show the new treatment
(6 mo) is noninferior or not worse than standard
treatment (12 mo) by more than 15% increase in the
DFS HR
• This would be accomplished if the CI does not
include 1.15 and the upper limit is less than 1.15
32
Slides reproduced from presentationPHARE conclusions
• Observed HR 1.28 (CI: 1.05-1.56) so inconclusive in
terms of noninferiority
• Since Lower CI > 1.0, conclude that 12 mo is better than
6 mo and increase in HR for 6 mo is at least 5%, not
sure if less than 15%
• 395 events much less than planned 1040 events, so if
trial had continued may have been able to statistically
show HR with 6 mo greater than 15% with tighter point
estimates
33
Slides reproduced from presentationADJUVANT TRASTUZUMAB
< 1 Year =
2 Years
6 Months
ONE YEAR ADJUVANT TRASTUZUMAB
REMAINS STANDARD
34
Slides reproduced from presentationHER2 franchise update Stefan Frings MD, Global Head Medical Affairs Oncology, Roche
Improving standard of care in HER2-positive
breast cancer in all lines of treatment
• PHARE and HERA confirm 1 year of Herceptin as SOC
• Subcutaneous Herceptin: HANNAH filed in 2012 (EU), device
Adjuvant BC: in development
• Perjeta APHINITY trial ongoing
• Plans for T-DM1 adjuvant program moving forward
• Perjeta (pertuzumab) approved in US, EMA approval
1st line mBC: expected in 2013
• CLEOPATRA showed significant PFS and OS benefit, final OS
data to be presented at SABCS 2012
• T-DM1 EMILIA submitted globally with medically and
2nd line / pre- statistically significant PFS. Statistically significant superior
treated BC: OS benefit observed in Aug 2012.
• US approval expected late 2012/early 2013
36Skin cancer franchise update Stefan Frings MD, Global Head Medical Affairs Oncology, Roche
Zelboraf
Annual incidence of patients with BRAF
mutated metastatic melanoma
28%
21% W-EU: 6’990 31%
N-AM: 5’410
LATAM:1’910
13%
8%
CEMAI: 7’700
APAC: 3’215
38
* Source: Globocan epidemiology & reported Mortality Rates(2008) with assumption of 50% BRAF mutation rateZelboraf in melanoma and beyond
Targeting BRAF-driven cancers to suppress
tumor formation
BRAF-mutation positive tumors
Metastatic melanoma Adjuvant melanoma
Vemurafenib monotherapy Vemurafenib monotherapy
BRIM8 Phase 3
• Patients with brain metastases (Ph2) FPI Q3/2012 NEW
MEK combination
• Zelboraf + MEKi RG7421 BRIM7 (Ph1)
Phase 3: FPI expected Q4/2012 NEW
Other combinations Other tumor types
• Zelboraf + ipilimumab (Ph1)
Vemurafenib monotherapy
• Zelboraf + anti PD-L1 RG7466 • Papillary thyroid cancer (Ph2)
NEW
Phase1: FPI Q3/2012
*RG7421=GDC-0973 39Phase 1B Study of Vemurafenib in Combination
with the MEK inhibitor,
GDC-0973, in Patients with Unresectable or
Metastatic BRAFV600-Mutated Melanoma
(BRIM7)
Rene Gonzalez,1 Antoni Ribas, 2 Adil Daud,3
Anna Pavlick,4 Thomas F. Gajewski,5 Igor Puzanov,6
Melinda S.L. Teng,7 Iris T. Chan,7 Nicholas Choong,7
Grant McArthur8
1University of Colorado Comprehensive Cancer Center, Denver, CO, USA;
2The Jonsson Comprehensive Cancer Center at University of California, Los Angeles, CA, USA;
3Hematology/Oncology Division, University of California, San Francisco, CA, USA;
4New York University Medical Center, New York, NY, USA; 5University of Chicago, Chicago, USA;
6Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 7Genentech, South San Francisco, CA, USA;
8Peter MacCallum Cancer Centre, East Melbourne, VIC, AustraliaAcquired resistance to
BRAF inhibition
MEK-dependent resistance MEK-independent resistance
NRAS mutations
RTK ligand
BRAFV600
BRAFV600 mutation overexpression
truncation / mutation RTK
amplification RTK overexpression
T
vemurafenib
COT overexpression
MEK PI3K
MEK mutations
T
RG7421
ERK AKT
Cell survival Cell survival
Corcoran RB, et al. Sci Signal 2010 23;3:ra84; Villanueva J et al. Cancer Cell 2010; Nazarian R et al. Nature 2010;
Su F et al. Cancer Res 2011; Wagle N et al. J Clin Oncol 2011; Johannessen CM et al. Nature 2010;
Poulikakos PI et al. Nature 2011
41
*RG7421=GDC-0973; in collaboration with ExelixisBRIM7 Results: Cohort Assignment
and Dose-limiting toxicity (6 July 2012)
Dose-escalation cohorts with GDC-0973 Dose-escalation cohorts with GDC-0973
dosed 14 days on/14 days off dosed 21 days on/7 days off or continuously
2A 5
100 mg n=3 60 mg
GDC-0973 daily
1C 1D
GDC-0973 daily
(28/0) n=3
(14/14)
2 4
80 mg n=4 n=5
60 mg 1A 1B
(21/7) n=8 n=6
1 3 Exp 1A Exp 1B
60 mg n=5 n=3 n=20 n=13
720 mg 960 mg 720 mg 960 mg
Vemurafenib twice daily Vemurafenib twice daily
As of 6 July 2012, 6 out of 10 dose cohorts have met the protocol-specified criteria to
be declared safe (cohorts shown in green in figures below)
One DLT observed in Cohort 1B: Gr 3 QT interval prolongation, related to vemurafenib
42BRIM-7 Results: AEs attributed to either
vemurafenib or GDC-0973 in all patients* (6 July 2012)
Most common AEs attributed to either vemurafenib or GDC-0973
n=70 Grade 3 or 4 Total
n % n %
Total number of patients with AEs 20 28.6 67 95.7
Non-acneiform rasha 5 7.1 37 52.9
Diarrhea 4 5.7 36 51.4
Photosensitivity / Sunburn 0 0 22 31.4
Fatigue 1 1.4 21 30.0
Nausea 1 1.4 20 28.6
Selected AEs attributed to either vemurafenib or GDC-0973
Creatine phosphokinase elevation 3 4.3 14 20.0
Liver function test elevationb 3 4.3 14 20.0
Arthralgia 1 1.4 9 12.9
Serous chorioretinopathyc 0 0 3 4.3
Cutaneous squamous cell carcinoma, KA 1 1.4 1 1.4
*Includes all patients reporting each of AE general terms, even for zero incidence.
aNon-acneiform rash includes MedDRA terms rash, rash generalised, rash maculo-papular, rash macular, rash papular,
rash erythematous, erythema, rash pruritic, dermatitis, skin exfoliation, dermatitis exfoliative, lividity
bLFT elevation includes MedDRA terms alkaline phosphatase increased, bilirubin increased, hyperbilirubinaemia, AST
& ALT increased, transaminases increased, and gamma-glutamyltransferase increased.
c Serous chorioretinopathy includes MedDRA terms chorioretinal disorder, chorioretinopathy, 1 pt with blurred vision
www.esmo2012.org
later diagnosed as serous choreoretinopathy.
43BRIM7 Results: Change in tumor size from
baseline to best response in BRAFi-naïve
patients
Best Tumor Response for Each Patient (BRAFi-naïve)
100
% Change from Baseline in SLD of Target Lesions
Cohort 1A
Cohort 1B
Cohort 1C
Cohort 2A
Cohort 4
50 Exp. Cohort 1A
Exp. Cohort 1B
0
-30
-50
-100
Individual Patients Treated with Vemurafenib and GDC-0973
SLD, sum of longest diameters n=25 evaluable patients
www.esmo2012.org
44BRIM7: Conclusions
GDC-0973 in combination with vemurafenib can be delivered
safely at the respective single-agent MTDs:
vemurafenib 960 mg BID, and
GDC-0973 60 mg QD 21 days on / 7 days off
Adverse events were tolerable and manageable
Preliminary anti-tumor activity in vemurafenib-naïve patients is
encouraging
Phase 3 study of vemurafenib + GDC-0973 is being initiated
45Open-label Pilot Study of Vemurafenib in
Previously Treated Metastatic Melanoma (Mm)
Patients (Pts) With Symptomatic Brain Metastases (BM)
Reinhard Dummer et al., Department of Dermatology, University Hospital of Zurich,
Switzerland
Responses in brain metastases
46Conclusions
Vemurafenib therapy:
feasible in patients with advanced melanoma with
symptomatic brain metastases
induces tumor regression in brain metastases in addition to
other sites of involvement
strong indications of vemurafenib activity in cerebral
metastases; efficacy and safety will be further studied with
longer-term follow-up
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