Clinical trials appendix

103 Pages·2015·2.15 MB·English

by  Gayle Stibbs

Clinical Trials Appendix
Q2 2015 Results Update
The following information about AstraZeneca clinical studies in Phases I-IV has
been created with selected information from clinicaltrials.gov to facilitate
understanding of key aspects of our clinical programmes and is correct to the best
of our knowledge as of 30 June 2015, unless otherwise specified.
It includes estimated timelines with regards to study completion and first external
presentations of primary data. These estimates are subject to change as
programmes recruit faster or slower than anticipated.
Project postings on clinicaltrials.gov are updated on a continuous basis as projects
progress. For the most up to date information on our clinical programmes please
visit clinicaltrials.gov.
List of abbreviations
AEs Adverse Events LCM Lifecycle Management Q3W Every Three Weeks
ASA Acetylsalicylic Acid LPD Last Patient Dosed Q4W Every Four Weeks
BiD Twice Daily MAD Multiple Ascending Dose Study Q8W Every EightWeeks
CE Clinically Evaluable MDI Metered Dose Inhaler QD Once Daily
cMITT ClinicalModified Intent-To-Treat population MITT Modified Intent-To-Treat population SAD Single Ascending Dose Study
DLT Dose Limiting Toxicity MicrobiologicalModified Intent-To- SC Sub-cutaneous
mMITT
Treat population
FEV Forced Expiratory Volume TiD Three Times a Day
MTD Maximum Tolerated Dose
FPD First Patient Dosed TOC Test of Cure
MTX Methotrexate
HIF- Hypoxia-inducible factor prolylhydroxylase XR Extended Release
PHI inhibitor NME New MolecularEntity
ICS Inhaled Corticosteroid OLE Open Long Term Extension
IM Intra-muscular ORR Objective Response Rate
IR Immediate Release OS Overall Survival
IV Intra-venous PARP Poly ADP ribose polymerase
LABA Long Acting Beta Agonist PFS Progression Free Survival
LAMA Long Acting Muscarinic Agonist Q2W Every OtherWeek
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Movement since Q1 2015 update
New to Phase I New to Phase II New to Pivotal Study New to Registration
NMEs NMEs
anifrolumab#1 CAZ AVI#
IFNαR SLE serious infections
PT0101 AZD9291 [US,EU]
LABA/LAMA/ICS COPD EGFREGFRmT790M NSCLC 2L+
Additionalindications Additionalindications Additionalindications
durvalaumab#+MEDI6383 durvalaumab#+tremelimumab AZD9291+durvalumab#
PD-L1+OX40 solid tumours PD-L1+CTLA-4gastric cancer durvalumab#+tremelimumab CONDOR¶
PT010 PD-L1+CTLA-4 2L SCCHN
LABA/LAMA/ICS asthma
Removed from Phase I Removed from Phase II Removed from Phase III Removed from Registration
NMEs LCM
tenapanor (AZD1722)# Nexium [JP]
NHE3ESRD-Pi/CKD with T2DM severe refractory oesphagitis2
Iressa[US]
EGFR EGFRmNSCLC3
# Partnered; ¶ RegistrationalPhase II/III trial
1 FPD July 2015; 2Submission withdrawn Q2 2015; 3FDA approved July 2015
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Q2 New Molecular Entity (NME)† Pipeline
RIA CVMD Oncology Infection, Neuroscience, Gastrointestinal
†Includes significant fixed dose combination projects, and parallel indications that are in a separate therapeutic area
(See LCM chart for other parallel indications and oncology combination projects)
# Partnered; ¶RegistrationalPhase II/III study
4 Note: PT010 COPD and anifrolumab SLE are Q3 2015 Phase III starts
Q2 Lifecycle Management (LCM)† Pipeline
RIA CVMD Oncology Infection, Neuroscience, Gastrointestinal
Oncology Combinations
Phase I Phase II Phase III
12 Projects 1 Project 2Projects
AZD9291+durvalumab durvalumab (MEDI4636)#+tremelimumab LaOdrgunrecv oamlluoomglyaeb cC u(oMlmeEDbIi4n6a3t6i)o# n+tsremelimumab Large molecule
(MEDI4636)#/selumetinib#/AZD6094# TATTON PD-L1+CTLA-4 gastric cancer ARCTIC
durvalumab (MEDI4636)# sequencing durvalumab (MEDI4636)# +tremelimumab
PD-L1 after EGFR/MEK/CTLA-4 NSCLC CONDOR¶
durvalumab(MEDI4636)#+dabrafenib+trametinibƔ
PD-L1+BRAF+MEK melanoma
durvalumab (MEDI4636)#+Iressa
PD-L1+EGFR NSCLC
durvalumab (MEDI4636)#+MEDI0680
PD-L1+PD-1 solid tumours
durvalumab (MEDI4636)#+MEDI6383#
PD-L1+Ox40 agonist solid tumours
durvalumab (MEDI4636)#+MEDI6469#
PD-L1+mOx40 solid tumours
durvalumab (MEDI4636)#+tremelimumab
PD-L1+CTLA-4 solid tumours
MEDI-551#+MEDI0680
CD19+PD-1 haems
MEDI-551#+rituximab
PD-L1+CD20 haems
MEDI6469#+rituximab
mOX40+CD20 solid tumours †Includes significant LCM projects and parallel indications for assets in Phase III or beyond. Excludes LCM projects
MEDI6469#+tremelimumab already launched in a major market
mOX40+CTLA-4 solid tumours # Partnered; ¶RegistrationalPhase II/III study; Ɣ MedImmune-sponsored study in collaboration with Novartis
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2015-2016:
14-16 NME & LCM submissions
MEDI4736 +
tremelimumab
2L SCCHN
Faslodex
MEDI4736
1L metastatic breast
2L SCCHN
cancer
LCM
Lynparza
Brilinta
submission BRCAm metastatic
stroke
opportunities breast cancer
Lynparza
saxa/dapa FDC  brodalumab*
BRCAm PSR
type2 diabetes psoriatic arthritis
ovarian cancer (SOLO-2)
Caprelsa
Brilinta  Bydureon lesinurad FDC
differentiatedthyroid
priorMI autoinjector gout
cancer
AZD6094MET (cMET)
CAZ AVI (CEPH/BLI) cediranib(VEGFR)
  papillary renal cell
serious infections ovarian cancer (EU)
carcinoma
NME
brodalumab*(IL-17R) selumetinib(MEK) X roxadustat (HIF) tremelimumab
submission
psoriasis uvealmelanoma CKD / ESRD (China) (CTLA-4)mesothelioma
opportunities
PT003 (LAMA/LABA) AZD9291 (EGFR T790) benralizumab(IL-5R) MEDI4736 (PD-L1)
COPD 2L NSCLC  severe asthma 3L NSCLC
2015 2016
*Amgen has announced that it has terminated development of brodalumab; AstraZeneca has announced it will confirm its decision on the future development of brodalumab
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Immuno-oncology
Major trials I
Tumour type Line of therapy Treme Combo Durva Combo OX40 Combo
(CTLA-4 mAb) durva+ treme (PD-L1 mAb) durva+ OX40 treme+ OX40
Mesothelioma Secondline DETERMINE
Phase II
NSCLC Adjuvant ADJUVANT
Phase III
Stage III un- PACIFIC
resectable Phase III
Firstline MYSTIC MYSTIC
Phase III Phase III
NEPTUNE + CTx
Phase III Phase III
EGFRm+ + Iressa
Phase III
Second line CAURAL
T790M + AZD9291
Phase III
Thirdline ARCTIC ARCTIC ARCTIC
Phase III Phase III Phase III
PD-L1+ ATLANTIC
PhII/single arm
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Immuno-oncology
Major trials II
Tumour type Line of therapy Treme Combo Durva Combo OX40 Combo
(CTLA-4 mAb) durva+ treme (PD-L1 mAb) durva+ OX40 treme+ OX40
SCCHN Secondline EAGLE EAGLE
PhaseIII PhaseIII
PD-L1- CONDOR CONDOR CONDOR
Phase II Phase II HAWK
PD-L1+ Phase II
Gastric Second/thirdline NAME TBD NAME TBD NAME TBD
PhaseII Phase II PhaseII
Pancreas Second line NAME TBD
Phase II
Bladder First line NAME TBD NAME TBD
Phase III Phase III
Melanoma - +BRAFi, MEKi
Phase I/II
Other advanced - + MEDI0680 MEDI6469 MEDI0562 MEDI6469
cancer (PD-1) (murine) (mAb) (murine)
Phase I Phase I/II MEDI6383 Phase I/II
(fusion protein)
Phase I
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AstraZeneca
Lifecycle management (new uses of existing medicines)
Lifecycle management
Late-stage development
Symbicort (ICS/LABA) Early development –IMED
Early development -MedImmune
Mild asthma
Patient population Study phase Number ofpatients Design Endpoints Status
Patients in need of GINA step Phase III N= 3,750 • Arm 1: Symbicort Turbuhaler 160/4.5 μg 'as needed' + Placebo • Well controlled asthma weeks • FPD: Q414
2 treatment SYGMA1 Pulmicort Turbuhaler 200 μg bid • Time to first severe asthma • LPD: 2017
• Arm 2: Pulmicort 200 μg Turbuhaler bid + terbutaline 0.4 mg exacerbation • Est. completion: 2017
NCT02149199 Turbuhaler 'as needed' • Time to first moderate or severe • Est. toplineresults: 2017
• Arm 3: terbutaline Turbuhaler 0.4 mg 'as needed' + placebo asthma exacerbation
Pulmicort 200 μg Turbuhaler bid • Average change from baseline in
pre-dose FEV1
Global study –19 countries
Patients in needof GINA step Phase III N = 4,114* • Arm 1: Symbicort Turbuhaler 160/4.5 μg 'as needed' + Placebo • Annualsevere asthma exacerbation • FPD: Q115
2 treatment SYGMA2 PulmicortTurbuhaler 200 μg bid rate • LPD: 2017
• Arm 2: Pulmicort200 μg Turbuhaler bid+ terbutaline0.4 mg • Time to first severe asthma • Est. completion: 2017
NCT02224157 Turbuhaler 'as needed' exacerbation • Est. topline results: 2017
• Average change from baseline in pre-
Global study –25 countries dose FEV1
• Timeto study specific asthma related
discontinuation
* There will be a blinded review for event rate which means that the final number of patients is uncertain until this review has taken place.
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