The OBR Blog

September 28, 2016 - 04:09 pm Posted in Featured comments0 Comments

By Cory Lewis, Ph.D., Manager, Clinical & Scientific Assessment, Kantar Health



We are in a unique time within cancer therapy, where significant resources are being used to develop drugs that target the immune system to fight cancer. Now we embark on a new endeavor in which most of the work is not discovering novel agents but developing a better understanding how to improve the use of therapies we have available.

Most of us are well aware of immunotherapy and its rise among the ranks of more than 3,400 cancer therapies. Immunotherapies targeting the immune checkpoint in cancer have led to the approval of Keytruda® (pembrolizumab, Merck), Opdivo® (nivolumab, Bristol-Myers Squibb), Yervoy® (ipilimumab, Bristol-Myers Squibb) and Tecentriq® (atezolizumab, Roche).

These immune checkpoint therapies are designed to inhibit those molecules that prevent the immune system pathway from acting on cancer cells, while immune costimulators are designed to activate the immune system.

Immune costimulators work by providing the signal that promotes the expansion and proliferation of killer CD8 and helper CD4 T-cells. While immune checkpoint therapies are “releasing the brakes,” costimulators are “stepping on the gas.” Both mechanisms are required for a robust immune system response.

The hope is that by combining checkpoint inhibitors with immune costimulators the immune response will be more robust and response rates will drastically increase. Many combinations are being evaluated to fine tune the immune system response while minimizing side effects.

Kantar Health’s newly developed CancerLandscapeTM platform identifies 23 immune checkpoint-targeted therapies in 893 trials in development, including 12 immune costimulators in 41 trials. Targets for immune costimulators include CD40L, GITR, 4-1BB, CD27, TNFRSF25, TMIGD2, ICOS, CD28 and OX40. Of this group, OX40 is the target furthest in development with over 12 ongoing clinical trials.

With all the new therapies and potential targets along with endless combination options it will be hard to decide which combinations are best to develop.

Some of these details are already being investigated:

  • The number of  times the immune system can be activated and still get a response
  • The stage of cancer in which it is best to use immunotherapy
  • The sequence of immunotherapy (i.e., CTLA4 then PD-L1, costimulators then checkpoint inhibitor,  vice versa, or both)

These details are currently being investigated in animal models and in the clinic and are important to the patients and their response to immunotherapy. The hope would be we can even unlock tumors not thought to be able to respond to immunotherapies by perfecting the system. The surface has just been touched when it comes to costimulators, and we all await the answers.

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