Combination of Immune Checkpoint Therapy with Targeted Therapy
In recent years, molecular treatments, such as immune checkpoint blockade and targeted therapy, have made great
progress. There has been considerable interest in the action mechanism of the immune checkpoint inhibitor and its
incorporation with other therapeutic regimens. The combination of immune checkpoint therapy with targeted therapy is
becoming a novel direction for the field of novel drug design.
Treatment with molecularly targeted therapy is associated with a high overall response rate but a limited duration
of response due to the emergence of therapeutic resistance. Conversely, treatment with immunotherapy is typically
associated with a lower response rate than that observed with targeted therapy. Given these limitations, there was
an increasing interest in combining targeted therapy and immunotherapy with the hope of achieving high response
rates with durable responses to therapy.
Response rate and duration of targeted and immunotherapy, as well as anticipated combination. (Prieto, 2016)
Combining Targeted Therapy and Immune Checkpoint Blockade
Combination therapy in cancer treatment is not a novel concept, as synergistic relationships have been revealed
across multiple lines of therapies, including hormonal, chemotherapy, and radiation therapies. Specifically, in
melanoma, developments in targeted therapy and immune checkpoint blockade overlapped significantly from a temporal
standpoint, and there was tremendous enthusiasm early on to empirically combine these treatment strategies to combat
the limitations of each of these strategies and enhance responses to therapy.
There are some ongoing clinical trials combining targeted therapy with either immune checkpoint blockade, radiation
therapy, or cellular therapy. Up to now, trials typically have used either a BRAF or immune checkpoint inhibitor
backbone with or without MEK inhibition. One of the first trials exploring the use of combined BRAF-targeted therapy
and immune checkpoint blockade began accruing patients in 2011 (NCT01400451). Several trials are now underway
evaluating the combination of targeted therapy and either PD1 or PD-L1 blockade (NCT01656642, NCT02027961,
As we move forward in combining immune checkpoint therapy with targeted therapy, it will be important to understand
the effects of each of the agents as monotherapy or in combination the tumor cells as well as the effects on other
components of the microenvironment. Creative Biolabs provides the following combination therapy
development for academic research.