It has been almost a decade since the US Food and Drug Administration (FDA) approved the first checkpoint inhibitor (CPI), Bristol Myers Squibb’s, YERVOY® (ipilimumab), in 2011. Since this initial approval, the number of clinical trials involving CPIs and other immuno-oncology (I-O) therapies has been exploding as drug developers investigate their use in combination with chemotherapy, radiotherapy, targeted therapies, cancer vaccines, oncolytic viruses, immunomodulatory agents and even other CPIs. As a result, there are now numerous I-O therapies and combinations of therapies under study with the goal of improving the rate, depth and duration of response in patients, while maintaining an acceptable level of toxicity.
While this combinatorial approach offers promise to patients by harnessing additive or complementary efficacy, the sheer number of potential therapy combinations and administration approaches pose challenges for drug developers. These range from complexity in trial design, biomarker selection, competition for patients and sites, potential for overlapping or unknown toxicities and commercial risks as the standard of care (SOC) is rapidly changing.
Here we highlight the issues that sponsors face in planning and executing combination I-O therapy trials and offer considerations to ensure that I-O trials are executed efficiently, safely and with the highest chance of success.