CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of analysis 3
Datamonitor insight into the molecular targeted therapies market 4
Related reports 5
Upcoming reports 5

CHAPTER 2 PIPELINE OVERVIEW AND DYNAMICS 7
Pipeline overview 7
Late-phase pipeline molecular targeted cancer therapies 7
Phase II pipeline molecular targeted cancer therapies 13
Phase I pipeline molecular targeted cancer therapies 27
Pipeline by developmental phase and class of drug 39
There are 373 different MTTs in clinical development 39
The cell cycle and apoptosis targeted agents is the largest class of MTT in the pipeline 40
Multi-targeted inhibitors account for the largest number of late-phase candidates while the single target agents will achieve higher level of sales 41
Pipeline by indication 42
Pipeline MTTs are being investigated in 42 different cancers 42
The 'big four' tumor types remain the most popular indications for development 45
Pipeline by mode of action 46
Pipeline products are directed against a huge variety and combination of molecular targets 46
Pipeline by company 48
There are 183 different companies developing targeted therapies 48
Top three companies in terms of number of pipeline MTT products are Pfizer, AstraZeneca and Novartis 49
Pfizer - 21 MTT pipeline products 49
AstraZeneca - 13 MTT pipeline products 51
Novartis - 13 MTT pipeline products 53
Key metrics 56
Datamonitor pipeline assessment summary 62

CHAPTER 3 CURRENT MARKET STATUS & PIPELINE CLASSIFICATION 68
Targeted therapies overview 68
The development of molecular targeted therapies 68
Current therapies are less cancer cell-specific 68
The strategy is to target the specific survival factors of a tumor 68
Key issue is the identification of targets unique to cancer cells 69
Market definition 69
L1X3 - Antineoplastic monoclonal antibodies 69
L1X9 - All other antineoplastics 70
Classification of pipeline products 71
Angiogenesis inhibitors 71
Angiogenesis as a normal biological process 71
Angiogenesis is known to be aberrant in tumor cell proliferation 72
Angiogenesis inhibitors as viable antitumor agents can target a number of pathways 73
At present, only one angiogenesis inhibitor exists on the market 74
Single-target signal transduction inhibitors 75
A plethora of potential targets exist along the signaling cascade 75
Several signal transduction inhibitors have reached the market, bringing with them their own sets of issues for consideration 75
Multi-targeted inhibitors 76
Multi-targeted inhibitors have certain advantages over single targeted agents 76
Approval of three multi-targeted inhibitors 77
Cell cycle and apoptosis targeted inhibitors 78
Only one cell cycle inhibitor has entered Phase III 78
Cell death can be induced via a number of different pathways 79
To date, only one apoptosis stimulator has reached the market 79
Immunomodulatory and immunoconjugated therapeutics 80
Antibody-based technologies are an effective anticancer approach 80
Epigenetic modulators 80
Despite relative immaturity of development in this class of drugs, the potential to enhance current therapies exists 81
Oncology clinical trial design 81
Patient selection 82
Increasingly significant in the era of targeted treatment 82
Clinical trial duration 83
Sufficient follow-up is necessary to establish true clinical benefit 83
The advent of novel therapies 83
Diversity of targeted therapies will require an evolution in clinical trial design 83
Clinical trial endpoints in oncology 84
Most oncology clinical trials designate multiple endpoints 84
Survival 84
Quality of life 84
Tumor response rates 85
Toxicity 85
Time to tumor progression 85

CHAPTER 4 PIPELINE ANGIOGENESIS INHIBITORS ANALYSIS & FORECASTS 87
Overview of angiogenesis inhibitors 87
Pipeline summary 87
Late-phase pipeline of angiogenesis inhibitors 87
Phase II pipeline of angiogenesis inhibitors 88
Phase I pipeline of angiogenesis inhibitors 90
Comparative forecasts to 2017 91
Drug assessment summary 94
Definition of current comparator therapy - Avastin (Bevacizumab; Genentech/Roche/Chugai) 95
Aflibercept (VEGF-Trap; Sanofi-Aventis/Regeneron) 96
Drug overview 96
Key historical events 97
Clinical trial data 98
Phase II results for aflibercept in advanced ovarian cancer 100
Interim Phase II results for aflibercept in NSCLC 102
Aflibercept demonstrates similar side effects to Avastin 102
Datamonitor comments 103
Fierce competition with Avastin in the wider cancer market 103
Presence in oncology field will aid commercialization of aflibercept 104
Armala (Pazopanib; GlaxoSmithKline) 105
Drug overview 105
Key historical events 106
Clinical trial data 106
Phase III trial evaluates Armala as a second-line monotherapy in metastatic RCC 109
Second Phase III trial compares Armala with Sutent head-to-head in the first-line RCC setting 111
Armala shows applicability across a broad range of solid tumor types 112
Datamonitor comments 114
Armala will face intense competition in the RCC market 114
Extensive parallel development program planned 115
Tykerb may well enhance the success of Armala but at what price? 115
Cilengitide (EMD-121974; Merck Serono) 116
Drug overview 116
Key historical events 116
Clinical trial data 117
Cilengitide may offer added benefit to standard treatment for glioblastoma multiforme 117
Datamonitor comments 119
Cilengitide is the only integrin antagonist in late-phase development...but is this enough? 119
Recentin (Cediranib, AZD2171; AstraZeneca) 119
Drug overview 119
Key historical events 121
Clinical trial data 121
AstraZeneca targets first-line CRC 124
Recentin's Phase II/III trial in advanced NSCLC does not progress into Phase III 126
Phase III study planned for Recentin in glioma 127
Datamonitor comments 128
Recent NSCLC results may have created skepticism regarding Recentin's future 128
Phase III studies in CRC are high-risk while development in glioma may offer a quicker route to market 128
AstraZeneca's strength in the oncology market will be key in Recentin's success 129
Ramucirumab (IMC-1121B; ImClone Systems) 129
Drug overview 129
Key historical events 129
Clinical trial data 130
Phase I data shows some evidence of antitumor activity 131
Datamonitor comments 132
A lack of clinical trial data makes it difficult to judge ramucirumab's potential 132
Will ramucirumab be able to compete with Avastin in the HER-2-negative breast cancer market? 132

CHAPTER 5 PIPELINE SINGLE-TARGET SIGNAL TRANSDUCTION INHIBITORS ANALYSIS & FORECASTS 133
Overview of single-target signal transduction inhibitors 133
Pipeline summary 133
Late-phase pipeline of single-target signal transduction inhibitors 133
Phase II pipeline of single-target signal transduction inhibitors 134
Phase I pipeline of single-target signal transduction inhibitors 136
Comparative forecasts to 2017 138
Drug assessment summary 142
Definition of current comparator therapy - Herceptin (Trastuzumab; Genentech/Roche/Chugai) 143
Afinitor (Everolimus; Novartis) 144
Drug overview 144
Key historical events 145
Clinical trial data 146
Afinitor is the first drug to show a clinical benefit in tyrosine kinase inhibitor-refractory RCC patients 147
Afinitor may be a promising addition to the treatment of neuroendocrine tumors 148
Afinitor is showing applicability in variety of tumor types 149
Datamonitor comments 155
Targeting a niche population, Afinitor will face lower barriers to market entry 155
Afinitor will have to significantly improve treatment outcomes in order to succeed in the neoadjuvant breast cancer setting 156
Novartis is an ideal backer for the drug 156
CP-751871 (Pfizer) 157
Drug overview 157
Key historical events 157
Clinical trial data 158
The combination of CP-751871 with chemotherapy is well-tolerated in a Phase II study 160
Datamonitor comments 162
Although costly, targeting multiple treatment settings in NSCLC may serve to maximize CP-751871's chances of approval 162
Deforolimus (ARIAD Pharmaceuticals/Merck & Co) 162
Drug overview 162
Key historical events 163
Clinical trial data 163
Phase III sarcoma trial now underway based on modest Phase I data 164
Datamonitor comments 166
Sarcoma offers a quicker route to market for deforolimus but is a higher risk strategy 166
Late-phase development of Avastin in sarcoma may pose a competitive threat for deforolimus 166
Deforolimus will also need to compete with Afinitor and Torisel in other oncology indications 167
Omnitarg (pertuzumab; Genentech/Roche/Chugai) 167
Drug overview 167
Key historical events 167
Clinical trial data 168
Phase II study suggests Herceptin-Omnitarg combination has activity in progressive metastatic breast cancer previously treated with Herceptin 169
Omnitarg has limited activity as a single agent in metastatic breast cancer with low HER-2 expression 170
The addition of Omnitarg to Gemzar produces no significant benefit over chemotherapy alone in platinum-resistant ovarian cancer 171
Omnitarg's development as a monotherapy in HRPC may have been discontinued 173
Datamonitor comments 174
Clinical benefit will have to outweigh increased cost of adding Omnitarg to Herceptin 174
Uncertainty as to whether Omnitarg will be developed for HER-2-negative population 174
TheraCIM (Nimotuzumab; YM Bioscience) 175
Drug overview 175
Key historical events 175
Clinical trial data 176
Nimotuzumab shows favorable toxicity profile in a Phase III study in pediatric pontine glioma 178
TheraCIM shows efficacy comparable to that of Erbitux in metastatic colorectal cancer 179
Pivotal trials planned for TheraCIM in NSCLC and brain metastases from NSCLC 180
Datamonitor comments 181
TheraCIM expected to gain approval in pediatric glioma 181
TheraCIM's potential in the oncology market can be greatly expanded 181
Improved toxicity profile will support TheraCIM's uptake 182
Xinlay (Atrasentan; Abbott Laboratories) 182
Drug overview 182
Xinlay's target receptor plays a key role in cancer cell proliferation 182
Key historical events 183
Clinical trial data 183
FDA does not approve Xinlay for prostate cancer 184
SWOG runs second Phase III trial in prostate cancer 185
Datamonitor comments 186
Despite its rejection by the FDA, Xinlay's future may still hold promise 186
Abbott's favorable position in the prostate cancer market will be invaluable 186
Zalutumumab (HuMax-EGFR; Genmab) 186
Drug overview 186
Key historical events 187
Clinical trial data 188
With Fast Track status granted, SCCHN offers promise as a lead indication for zalutumumab 190
Datamonitor comments 191
A head-to-head study against Erbitux could work in zalutumumab's favor 191
Zalutumumab may have to compete with Tarceva and Iressa 192
Zalutumumab may also have to compete with Tarceva and Iressa 192
Zarnestra (Tipifarnib; Johnson & Johnson) 192
Drug overview 192
Key historical events 192
Clinical trial data 193
Following rejection of NDA, the FDA requires Phase III data for Zarnestra in AML before regulatory approval can be considered 195
Zarnestra fails to increase overall survival compared to BSC in a Phase III study 196
Zarnestra has been evaluated in a number of Phase II studies 197
Single-agent Zarnestra demonstrates antitumor activity in relapsed/refractory aggressive NHL 200
Zarnestra holding promise in juvenile myelomonocytic leukemia 201
Negative Phase III trial results cause termination of development in pancreatic and colorectal cancer 202
Datamonitor comments 204
Zarnestra's Phase III trial results raise more concerns regarding its future 204

CHAPTER 6 PIPELINE MULTI-TARGETED INHIBITORS ANALYSIS & FORECASTS 205
Overview of multi-targeted inhibitors 205
Pipeline summary 205
Late-phase pipeline of multi-targeted inhibitors 205
Phase II pipeline of multi-targeted inhibitors 207
Phase I pipeline of multi-targeted inhibitors 209
Comparative forecasts to 2017 210
Drug assessment summary 215
Definition of current comparator therapy - Gleevec (Imatinib; Novartis) 216
Axitinib (AG-13736; Pfizer) 217
Drug overview 217
Key historical events 218
Clinical trial data 218
Phase III trial initiated in pancreatic cancer following a 26% reduction in the risk of death in a Phase II trial 220
Activity in Nexavar-refractory RCC patients drives Phase III development in the second-line setting 220
Axitinib demonstrates impressive activity in thyroid cancer but Phase III trial has yet to start 221
Axitinib also making progress in other popular tumor types 222
Datamonitor comments 225
A similar response rate to Tarceva in pancreatic cancer suggests approval will be likely 225
Head-to-head Phase III trial against Nexavar could maximize axitinib's potential 226
Axitinib will enjoy Pfizer's global presence and unparalleled marketing strength 226
Bosutinib (SKI-606; Wyeth) 226
Drug overview 226
Key historical events 227
Clinical trial data 227
Bosutinib Phase II results in Gleevec-resistant/intolerant chronic phase CML 228
Bosutinib Phase II results in Gleevec-resistant/intolerant accelerated phase (AP) and blast crisis (BC) CML and Ph+ ALL 230
Datamonitor comments 232
The CML market is comparatively well served by Gleevec, Sprycel and Tasigna 232
Like the others, bosutinib appears ineffective in patients harboring the T315I mutation - a key driver of resistance 232
Bosutinib trying to catch up with Sprycel and Tasigna in the race to replace Gleevec in the front-line setting 232
Brivanib (BMS-582664; Bristol-Myers Squibb) 233
Drug overview 233
Key historical events 233
Clinical trial data 234
Brivanib and Erbitux competition shows early signs of clinical activity in a Phase I study 235
Datamonitor comments 237