FIGURE 1: Active, commercial immuno-oncology trials.   (SOURCE: Cortellis Clinical Trials)

Checkpoint Inhibitors

On the opposite end of the spectrum, checkpoint inhibitor trials are exhibiting a rapid-fire growth pattern and tremendous success. Since 2010, they have experienced a twenty-fold increase in the number of commercially relevant trials as compared to those started in 2015. Anti-CTLA-4 trials comprise a quarter of the current space, while target newcomers, PD-1 and PD-L1, make up the remainder, with PD-1 being studied in more than half of current trials.

PD-1 is a receptor on T-cells and binds ligands PD-L1 and PD-L2 to prevent T-cell activation. Upregulation of these proteins causes cancer cells to go unnoticed by the immune system. Inhibiting this checkpoint, however, lifts the veil, allowing the immune system to launch an attack. Both big pharma and biotech companies are active in the space and are taking on trials at almost double the rate of therapeutic vaccines.

BMS, following up on their success with Yervoy (CTLA-4) and Opdivo (PD-1), are at the top of the space, followed by Merck (Keytruda, PD-1) and Roche. Early and late phase trials are split down the middle indicating both interest in the space and successful progression to phase III trials. Until recently, melanoma has been the top indication in the space; however it has since been surpassed by lung cancer.

Advanced metastatic cancers, those where other treatments have failed, remain the top patient segments in checkpoint inhibitor trials. Challenges in this space lie in identifying predictive and prognostic biomarkers. Correlating response rate to the PD-L1 biomarker, which is currently seen in 39 percent of checkpoint inhibitor trials measuring biomarkers, is not always possible.


Immuno-oncology is a highly marketable and dynamic space currently led by checkpoint inhibitors. However, as niches become saturated, developers must look to identify novel approaches. Immunotherapy and cross-class combinations are proving to be successful, and the recent approval of Amgen’s oncolytic virus (T-vec) for inoperable melanoma is giving hope that there are opportunities beyond T-cells. Our immune system is a complex defense structure full of cells ready to take on the fight against cancer – they just need the right orders.