Susanna Varkey Ulahannan, MD, The University of Oklahoma College of Medicine, Oklahoma City, OK, talks on the unanswered questions in in the use of immunotherapy in colorectal cancer (CRC). A predominant issue is the identification of subsets of patients who have an excellent response to treatment. In the platform trial (NCT03697304) exploring ezabenlimab plus a VEGF/ANG2-blocking nanobody, BI 836880, in patients with advanced microsatellite stable (MSS) CRC, the difference in benefit between metastatic and non-metastatic liver disease was explored, however no difference was observed. These results were in contrast to another trial presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium 2022 investigating pembrolizumab plus regorafenib in MSS CRC. Although they did not observe any partial responses, unlike in the platform trial, they observed a benefit via subgroup analysis in patients who did not have liver disease versus those who did. Additionally, patients who had undergone prior radiotherapy appeared to benefit from the immunotherapy and TKI combination. In the platform trial investigating ezabenlimab plus BI 836880, paired biopsies are being carried out before and after treatment to identify which patients benefit from treatment. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium 2022.