The global cancer immunotherapy pipeline continues to explode with nearly double the number of active targets in 2019 vs. only two years ago, comprising 3,876(!!) active drugs, with a subset undergoing >5000 active clinical trials.

In 2016, I listened to Dan Chen, former Global Head of Cancer Immunotherapy Development at Genentech, comment on the challenge of enrolling patients in immunotherapy trials with nearly 1000 trials competing for patients.  Only three years later, it’s shocking and amazing to see that there are >5000(!!) active clinical trials on-going for immunotherapy agents worldwide.

According to this excellent article by Jun Tang and colleagues in Nature Reviews Drug Discovery,1 the majority (3428) of these clinical trials are evaluating T cell-targeted immunomodulators, which includes the PD-1/L1 and CTLA-4 checkpoint inhibitors (Figure 1).

Distribution of immunotherapy clinical trials by modality
Figure 1. Number of clinical trials by therapy type. From J. Tang, et al., Nat. Rev. Drug. Discov.; doi: 10.1038/d41573-019-00167-9

While the number of clinical trials is heavily weighted by what’s known to be working (T-cell modulation), the distribution among the number of new agents has not changed significantly (Figure 2). The only major change is a greater shift from cancer vaccines which have not seen as much clinical success, to cell therapies which have seen significant success in liquid tumors.

Distribution of investigational immunotherapy agents by modality
Figure 2. Change in distribution of agents by mode of action from 2017 to 2019.

Fortunately, despite the rush into T-cell immunomodulators like anti-PD-1 and IDO1, the global pipeline is growing significantly in mechanistic diversity as well.  Whereas there were 263 publicized active targets in 2017, there were more than 468 publicized active targets in 2019, with likely many more undisclosed (Figure 3).

Summary of active immunotherapy targets in 2017 vs 2019
Figure 3. Number of publicly disclosed immunotherapy targets with bubble size weighted by number of unique agents. Adapted from J. Tang, et al., Nat. Rev. Drug. Discov.; doi: 10.1038/d41573-019-00167-9

The new targets also fall within different buckets – while the number of active targets for T-cell targeted immunomodulators have experienced the largest percent growth (347%), the largest bucket for targets in absolute terms is “other immunomodulators” at 183 targets (Figure 4).  This presumably reflects the growing interest in compartments such as the innate immune system, suppressor cells, and antigen presenting cells.

Number of unique immunotherapy targets by therapy type
Figure 4. Number of unique IO targets by therapy type. From J. Tang, et al., Nat. Rev. Drug. Discov.; doi: 10.1038/d41573-019-00167-9

It’ll be fascinating to watch this field and see what among these become part of the standard of care in cancer in 2029. The source article is well-written and easy read, with thought-provoking figures – go take a look!

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