N E W S & A N A LY S I S

FROM THE ANALYST’S COUCH

Trends in the global

immuno-oncology landscape
Jun Tang, Laura Pearce, Jill O’Donnell-Tormey and
Vanessa M. Hubbard-Lucey Blue armchair by onurdongel/iStock/Getty Images Plus

The approval of ipilimumab in 2011 to treat

melanoma marked the beginning of the T cell-targeted 2018 419 85 49 76%
immunomodulator 2017 223 60 36 increase
cancer immunotherapy revolution, which Other 2018 581 63 85 79%
has progressively changed the paradigm immunomodulator 2017 262 66 64 increase
Therapy type

Cancer vaccine 2018 397 145 228 33%

of cancer care in recent years. Since then, 2017 261 130 178 increase
11 new cancer immunotherapies have been Cell therapy 2018 448 176 227 113%
2017 179 112 109 Development stages increase
approved, and these new therapies have 2018 137 27 16%
Oncolytic virus Approved Phase I
quickly become the standard of care for 2017 95 34 increase
CD3-targeted 2018 125 28 Phase III Preclinical 98%
many cancer types. bispecific mAb 2017 47 29 Phase II increase
To inform the cancer immunotherapy
0 100 200 300 400 500 600 700 800 900
community of the advances in the rapidly
evolving field, the Cancer Research Number of active IO agents
Institute, a nonprofit group dedicated to Figure 1 | Trends in the global IO pipeline. 3,394 agents were identified in six main classes in
Nature Reviews | Drug Discovery
research in cancer immunotherapy for more September 2018, an increase of 67% since the previous survey. IO, immuno-oncology; mAb,
than 65 years, conducted a comprehensive mono­clonal antibody.
survey of the global immuno-oncology
(IO) landscape in September 2017 (Ann.
Oncol. 29, 84–89; 2017). One year later, 16% increase. By September 2018, cell agents in all classes (1,067 versus 2,107;
in September 2018, we have conducted therapies had surpassed cancer vaccines as 97% increase) is greater than that of clinical
another landscape survey. In this report, the largest IO drug class, with 864 active agents (964 versus 1,287; 34% increase),
we compare the two surveys and provide agents, comprising 25% of all IO agents. suggesting growing innovation in basic and
longitudinal analyses of the evolution of Additionally, the growth of preclinical preclinical research. ▶
the global IO landscape.
2018 7 106
Trends in the IO landscape CD19 2017 5 87
Growth of the global IO pipeline. In the past 2018 5 95
PD1 2017 3 88
year (September 2017 to September 2018), 2018 6 6 72
PDL1 2017 7 4 60
there was a 67% increase in the number of
HER2 2018 9 22 34
active agents in the global IO pipeline (2,031 2017 7 17 28
versus 3,394; FIG. 1). We organized these STAT3 2018 47
2017 32
agents into six classes, based on different 2018 18 23
NY-ESO-1 2017 7 18
mechanisms of action: first, T cell-targeted
2018 5 34
immunomodulators (for example, CTLA4 2017 29
Target

monoclonal antibodies against PD1 or IDO

2018 3 6 27
2017 33
CTLA4); second, other immunomodulators 2018 9 25
BCMA
(for example, agonists against toll-like 2017 6 14
2018 33
receptors (TLR) or interferon-α/β receptor Neoantigen
2017 14
1 (IFNAR1)); third, cancer vaccines (for CSF1R 2018 32
2017 27 Therapy type
example, bacillus Calmette–Guérin (BCG) 2018 8 23
WT1
vaccine); fourth, cell therapies (for example, 2017 4 16 T-cell targeted immunomodulator
chimeric antigen receptor (CAR) or T cell 2018 7 23 Other immunomodulator
MUC1 2017 6 18 Cancer vaccine
receptor (TCR) T cell therapies); fifth, CD47
2018 30 Cell therapies
oncolytic viruses (for example, T-vec); and 2017 19 Oncolytic virus
2018 30 CD3-targeted bispecific mAb
sixth, CD3-targeted bispecific antibodies TLR7 2017 25
(for example, blinatumomab). Of the six
0 10 20 30 40 50 60 70 80 90 100 110 120
different classes, the cell therapy class had
the largest growth — a 113% increase in Number of active IO agents
the number of active agents — whereas Figure 2 | Trends in IO targets. The top 15 of a total of 417 immuno-oncology targets in the current
Nature Reviews | Drug Discovery
oncolytic viruses had only a modest pipeline, a 50% increase since the previous survey. IO, immuno-oncology; mAb, monoclonal antibody.

NATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | NOVEMBER 2018 | 783

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 N E W S & A N A LY S I S

FROM THE ANALYST’S COUCH

▶ More targets in IO pipeline. In the past year, 2018 6 13 2 2
Bristol-Myers Squibb 2017 5 8 2
the number of IO targets with active agents
2018 13 7
increased by 50%, with 417 targets now in the Celgene 2017 11 4
current global IO pipeline (Supplementary 2018 9 7 1 2
Novartis 2017 11 5 1 2
Table 1). Interestingly, whereas the top 23 AstraZeneca/ 2018 10 5 1 1
targets attracted half of the agents in the MedImmune 2017 9 5 1 1
2018 9 4 3
previous pipeline, we found that half of the Roche/Genentech
2017 13 2 1 3
agents in the current pipeline spread across Merck & Co.
2018 8 1 5
2017 7 2 5
the top 48 targets (Supplementary Table 1). 2018 9 1 1 2

Company
Amgen
In general, targets with already approved 2017 7 1 1 2
2018 6 6 1
agents attracted fewer new agents in the past Gilead Sciences 2017 5 7
year than those without approved agents National Cancer 2018 7 6
Institute 2017 5 1
(FIG. 2). For example, despite a 113% increase 2018 5 7
GlaxoSmithKline Plc
in the number of cell therapies in a year, 2017 4 8
Shenzhen Geno-Immune 2018 12
CD19-targeted cell therapies only increased Medical Institute 2017 1 5
by 37%. Conversely, the number of agents China PLA General 2018 5 4 1
Hospital 2017 3 3
targeting neoantigens (for example, targets 2018 6 2 2 Clinical stages
identified through bioinformatic analysis of an Eli Lilly 2017 5 2 Approved
individual patient’s tumour) increased by 133% Johnson & Johnson 2018 6 3 1 Phase III
2017 6 4 Phase II
in 1 year. The increase in the number of targets Third Military Medical 2018 1 9 Phase I
being addressed by IO agents may lead to a University Hospital One 2017 8
broader range of approved immunotherapies 0 2 4 6 8 10 12 14 16 18 20 22 24
in the future. It is worth noting that agents Number of active IO agents
against non-specified tumour-associated
antigens (TAA) actually showed a decrease in Figure 3 | Trends in organizations with IO agents in clinical development. The current top 15
Nature Reviews | Drug Discovery
clinical pipelines in immuno-oncology (IO) from total 655 clinical-stage organizations, which jointly
the number of active agents, suggesting that
own 1,297 IO agents in clinical stage.
the field is moving in more precise directions
(Supplementary Fig. 1).
2017, the FDA has granted two approvals to primary factor to guide IO drug development.
More organizations now in global IO CAR T therapies, eight approvals to anti-PD1 For example, biomarkers should be adopted
development. In September 2017, 461 and anti-PDL1 agents, and one approval for for all eligible cancer trials to identify those
organizations (including both academia a CD3-targeted bispecific antibody, totalling patients who may most likely benefit from
and industry) were developing 964 clinical 10 approvals in one year. Second, since 2011, the right novel cancer immunotherapies.
agents. One year later, 655 organizations are new immunotherapies have become not only In addition, correlative studies should be
developing 1,287 clinical agents, which means the standard of care for 15 cancer types, but maximally integrated into all clinical trials
a 42% increase in the number of clinical also the front-line treatments for melanoma, so we can learn both from successful and
stage organizations and a 34% increase in lung cancer and kidney cancer, making failed clinical trials, which would allow every
the number of clinical-stage agents (FIG. 3). immunotherapy one of the pillars of cancer clinical trial and every patient volunteer to
Focusing on the top 15 clinical pipelines, therapy. Third, immunotherapies, such as make increased contributions to our pursuit
we found that 36 new agents were added anti-PD1 and anti-PDL1 agents, are quickly of cures for cancer.
in 1 year, a 20% increase. Importantly, big entering into major markets beyond the
pharma still dominates the clinical space, United States, Europe and Japan, exemplified Jun Tang*, Laura Pearce, Jill O’Donnell-Tormey and
Vanessa M. Hubbard-Lucey are at the Anna-Maria
as the top 8 clinical pipelines all rest with by the recent approvals of nivolumab
Kellen Clinical Accelerator, Cancer Research Institute,
major pharmaceutical companies. However, and pembrolizumab in China. Finally, a New York, NY, USA.
4 academic centres made the top 15 clinical large number of clinical studies prove that *e-mail: clinicalacceleratorIO@cancerresearch.org
pipelines. immunotherapies bring long-lasting survival
doi:10.1038/nrd.2018.167
benefits to patients, fulfilling the promise of Published online 19 Oct 2018
Conclusion cancer immunotherapy as a potential cure
Competing interests
Our landscape analyses show that, in 1 year, for some cancer patients. J.O-T. is a paid board member of HemaCare. L. P. is a con-
the IO global pipeline had a 67% increase in However, caution is needed when sultant to Cancer Research Institute and Canadian Cancer
Trials Group.
the number of active agents, a 50% increase in translating the promising science of
Supplementary information
active drug targets and a 42% increase cancer immunology into successful cancer Supplementary information is available for this paper at
in active clinical-stage organizations. immunotherapies. The recent failure or https://doi.org/10.1038/nrd.2018.167
This tremendous growth suggests a termination of multiple phase III studies
strong enthusiasm in, and an unparalleled evaluating indoleamine 2,3-dioxygenase 1 RELATED LINKS
commitment to, IO drug development. (IDO1) inhibitors reminds us that drug Cancer Research Institute Clinical Accelerator:
www.cancerresearch.org/IO-landscape
We think this optimism is well justified. development is a very risky endeavour. Going
ALL LINKS ARE ACTIVE IN THE ONLINE PDF
First, since our last survey in September forward, scientific evidence should be the

784 | NOVEMBER 2018 | VOLUME 17 www.nature.com/nrd

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