Gsk Plc · LSE:GSK
Gsk — ESMO 2012 Analyst Briefing
28 slides from Gsk's conference presentation, Oct 1, 2012
Slide 1: ESMO Briefing
ESMO Briefing Paolo Paoletti, MD President, GSK Oncology
Slide 2: Since ASCO
S Since ASCO SCO • Promacta/Revolade ® study in aplastic anaemia published in New England Journal of Medicine • Withdrawal of Tykerb/Tyverb ® FDA application for dual blockade • EU approvall ffor Votrient V t i t ® in i advanced d d soft ft titissue sarcoma • Dabrafenib monotherapy submissions in US
Slide 3: Our Oncology Growth
O Growth Our G 800 700 600 Mature Products 500 Growth Products 400 GSK 300 Oncology in H1 2012 was 200 £375m +22% CER 100 0 2007 2008 2009 2010 2011 3
Slide 4: Key ESMO Highlights
Key ESMO S O Highlights • Combination Dabrafenib+Trametinib – Randomised, open-label data for dabrafenib alone vs combination in pts with BRAF V600 mutation-positive metastatic melanoma • Votrient® – Results of the COMPARZ trial – Results of HRQoL data from PALETTE – Quality of life (QoL) in renal c
Slide 5: Dabrafenib+Trametinib Phase II Randomised Data: Study 113220
Dabrafenib+Trametinib Phase II Randomised Data: Study 113220 Dr. Georgina Long, BSc, PhD, MBBS, FRACP Westmead Hospital and the Melanoma Institute A stralia Australia
Slide 6: Combined BRAF and MEK Inhibition in Melanoma (NEJM)
wd , 2 te NEW ENGLAND S JOURNAL of MEDICINE ORIGINAL ARTICLE Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations Keith T. Flaherty, M.D., Jeffery R. Infante, M.D., Adil Daud, i.D., Rene Gonzalez, M.D., Richard F. Kefford, M.D., Ph.D., Jeffrey Sosman, M.D., Omid Hamid, W.D., Lynn Sc
Slide 7: Randomised Phase II study of dabrafenib vs combination with trametinib
Randomised Phase II study of BRAF inhibitor dabrafenib vs combination with MEK inhibitor hb trametinib b in BRAF V600 mutant metastatic melanoma G.V. Long, J. Sosman, A. Daud, J. Weber, K. Flaherty, J. Infante, O. Hamid, L. Schuchter, J. Cebon, I. Puzanov, A. Algazi, R. Kudchadkar, K. Lewis, W. Hwu,
Slide 8: Rationale for Combination
Rationale for Combination RAS BRAFi (dabrafenib) BRAF mutBRAF PFS 5.1 mo; RR 53%1 Preclinical P li i l BRAFi +MEKi MEKi Delays BRAFi resistance MEKi (trametinib) MEK Hyperproliferative skin AE OS HR 0.54 v chemo h PFS 4.8 mo; RR 22%2 pERK Proliferation Survival Invasion Metastasis www.esmo2012.org
Slide 9: Part C Randomised Phase II Study Design
Part C Randomised Phase II Study Design R Monotherapypy D 150mgg BID* •BRAF V600E/K metastatic A N= 54 melanoma N •No prior BRAFi or MEKi D Combination D+T 150/1 •Up to 1 prior treatment O N= 54 •Treated Treated and stable brain mets M I Combination D+T 150/2 N=162 S N= 54 E *cross over to Combinati
Slide 10: Confirmed Response Rate
Confirmed Response Rate Combination D+T Combination D+T Mono D 150/1 150/2 (N=54) (N=54)* (N=54) CR 2 (4) 3 (6) 5 (9) PR 27 (50) 24 (44) 36 (67) SD 22 (41) 24 (44) 13 (24) PD 3 (6) 2 (4) 0 Response Rate† 29 (54%) 27 ((50%)) 41 ((76%)) p=0.77 p=0.026 Duration of Response 5.6 9.5 10.5 Months (95% CI)
Slide 11: Progression-Free Survival
Progression‐Free Survival Med HR (95% CI) CI), 12 mo. 1.0 (mos) P‐Value PFS rate Mono D 5.8 9% 0.8 150/1 / 9.2 0 56 (0 0.56 (0.37, 37 00.87), 87) 0.006 0 006 26% 150/2 9.4 0.39 (0.25, 0.62),<0.0001 41% val function n 0.6 04 0.4 ated surviv 0.2 Estima Med follow up time 14 mo 0.0 0 3 6 9 12 15 18 Pat
Slide 12: Overall Survival
Overall Survival 12 mo. OS Median HR, P‐Value rate Mono D NR 70% 150/1 NR 0.98, NS 68% 1.0 150/2 NR 0.67, NS 79% nction 0.8 stimated survival fun 0.6 0.4 Med follow up time 14 mo 0.2 Es 43/54 (80%) Monotherapy M th D crossed d to t 150/2 0.0 0 3 6 9 12 15 18 Patients at risk Time since randomization
Slide 13: MEKi and BRAFi Associated Adverse Events
MEKi and BRAFi Associated Adverse Events Combination D+T Combination D+T Monotherapy D 150/1 150/2 (n=53) (n=54) (n=55) Alopecia 16 (30) 2 (4) 3 (5) Skin papilloma 8 (15) 4 (7) 2 (4) Hyperkeratosis 16 (30) ( ) 3 (6) ( ) 5 (9) ( ) Squamous cell carcinoma/ 10 (19) 1 (2) 4 (7) keratoacanthoma 0 004 0.0
Slide 14: Treatment-Related AEs ≥ 20% (All Grades)
Treatment‐Related AEs ≥ 20% (All Grades) Monotherapy D Combination D+T 150/1 Combination D+T 150/2 ((n=53*)) ((n=54)) ((n=55*)) Pyrexia† 12 (23) 34 (63) 37 (67) Chills 9 (17) 22 (41) 28 (51) Night Sweats 3 (6) 8 (15) 12 (22) Fatigue 18 (34) 25 (46) 25 (45) Arthralgia 14 (26) 22 (41) 14 (25) Myalgia
Slide 15: Conclusions
Conclusions This is the 1st kinase‐kinase combination to: Show enhanced anti‐tumour activity over the single agent Reduce specific oncogenic toxicities toxicities, with biological rationale Combined dabrafenib and trametinib prolongs PFS and ORR over dabrafenib alone in BRAFV600 600 metastat
Slide 16: COMPARZ
COMPARZ Dr. Paul Nathan MBBS, PhD, FRCP Consultant Medical Oncologist Director R&D Mount Vernon Cancer Centre, UK
Slide 17: Study Objectives
Study Objectives Primary • To evaluate and compare PFS in patients treated with pazopanib to those treated with sunitinib S Secondary d • Overall survival (OS) • Objective response rate (ORR) • Safety • Patient-reported outcomes
Slide 18: Study Design
Study Design Pazopanib 800 mg qd continuous dosing Dose reductions to 600 mg or 400 mg Key y Eligibility g y Criteria • Advanced/metastatic RCC • Clear-cell histology • No prior systemic therapy Randomized • Measurable disease (RECIST 1.0) 1:1 • KPS ≥ 70 • Adequate organ function Sunitinib 50 mg qd
Slide 19: Statistical Analysis Plan
Statistical Analysis Plan • PFS S non-inferiority o e o ty dedemonstrated o st ated if uppe upper bou bound doof 95% CI for HR<1.25 – Cox proportional hazard analysis adjusted for stratification factors – By independent review • 631 PFS events needed for 80% power • Planned enrollment of 1100 patien
Slide 20: Primary Endpoint: Progression-free Survival (independent review)
Primary Endpoint: Progression-free Survival (independent review) N Median PFS (95% CI) P Pazopanib ib 557 8 4 mo (8 8.4 (8.3, 3 10 10.9) 9) Sunitinib 553 9.5 mo (8.3, 11.1) HR (95% CI ) = 1.047 (0.898,1.220) Pazopanib Sunitinib
Slide 21: Primary Endpoint: Progression-free Survival (independent and investigator review)
Primary Endpoint: Progression-free Survival (independent and investigator review) Independent HR (95% CI ) = 1.047 (0.898,1.220) Investigator HR (95% CI ) = 0.998 (0.863,1.154)
Slide 22: Best Response by RECIST 1.0
Best Response by RECIST 1.0 (independent review) Pazopanib Sunitinib ((n = 557)) ((n = 553)) Best overall response, % Complete C l t response (CR) <1 <1 Partial response (PR) 31 24 S bl di Stable disease 39 44 Progressive disease 17 19 Not evaluable 13 12 Objective j Response p Rate,, % 31 25 95% CI
Slide 23: Interim Analysis of Overall Survival
Interim Analysis of Overall Survival N Median OS (95% CI) Pazopanib 557 28.4 mos (26.2, 35.6) Sunitinib 553 29.3 mos (25.3, 32.5) HR (95% CI ) = 0.908 (0.762,1.082) P-value = 0.275 Pazopanib Sunitinib
Slide 24: Most Common Adverse Events
Most Common Adverse Events Pazopanib (n = 554) Sunitinib (n = 548) % % Adverse Event a All Grs All Grs Any event b >99 >99 Di h Diarrhea 63 57 Fatigue 55 63 Hypertension 46 41 Nausea 45 46 Decreased appetite 37 37 ALT increased 31 18 Hair color changes 30 10 Hand-foot syndrome 29 50 Taste Alteration
Slide 25: Relative Risk in Adverse Events
Relative Risk in Adverse Events AE occurrence ≥10% in either arm; 95% CI for RR does not cross 1 Hair color change Weight decreased S Serum ALT increased i d Alopecia Upper abdominal pain Serum AST increased Fatigue * Rash * Pain in extremity Constipation Taste Alteration * LDH increased Serum creat
Slide 26: Quality of Life Results (first 6 months)
Quality of Life Results (first 6 months) Treatment difference in Instrument Domain Name mean change vs P ‐value sunitinib1 FACIT-F Fatigue/Total score 2.32 <0.001 Kidney Symptom Index/Total score 1.41 0.018 Physical 0.78 0.027 FKSI 19 FKSI-19 Emotional –0.05 0 05 0 409 0.409 Treatment Side Effects 0
Slide 27: Conclusions
Conclusions • This phase III trial demonstrates non-inferiority of pazopanib relative to sunitinib for progression-free survival • Pazopanib efficacy is further supported by similar response rates and overall survival • The differentiated safety profile of pazopanib includes: – Lower o e incidence c
Slide 28: Questions?
e cs Oncology Questions?