Dr Li on the Utility of ADG126 Plus Pembrolizumab in MSS CRC

Daneng Li, MD, associate professor, Department of Medical Oncology and Therapeutics, research co-director, Neuroendocrine Tumor Program, City of Hope, discusses the implications of a phase 1b/2 study (NCT05405595) evaluating ADG126 in combination with pembrolizumab (Keytruda) in patients with metastatic microsatellite-stable (MSS) colorectal cancer (CRC).

At the 2024 Genitourinary Cancers Symposium, Li and coinvestigators presented research focusing on the use of the anti-CTLA4 monoclonal antibody ADG126 in patients with CRC. This monoclonal antibody plays a crucial role in penetrating the tumor microenvironment, thereby providing enhanced exposure to the tumor and simultaneously minimizing systemic toxicities, Li begins. Initially, the investigation encompassed all solid tumors during the dose-escalation portion, he reports. However, investigators have now transitioned into the dose-expansion portion of the investigation, specifically concentrating on patients with MSS metastatic CRC, a patient cohort characterized by significant unmet medical needs, Li explains.

Looking to the future of this investigation, Li goes on to say that he and coinvestigators aim to move forward with the dose-expansion strategy for patients with MSS CRC who do not exhibit liver metastasis. Moreover, considering the favorable safety and tolerability profile observed with ADG126 plus pembrolizumab, further dose-escalation strategies may be employed in the future, Li emphasizes. The safety profile of this combination contrasts notably with those of traditional CTLA4-targeting treatment approaches, indicating a promising avenue for dose escalation, he states.

The encouraging safety and tolerability profile of this combination, coupled with observed efficacy, provide a solid foundation for additional expansion endeavors and potential dose escalation in the future, Li continues. By administering ADG126 every 3 weeks in conjunction with pembrolizumab, Li and coinvestigators anticipate fostering an environment conducive to enhancing the efficacy of immuno-oncology in patients with CRC, particularly for those traditionally considered to have a “cold tumor” phenotype, he adds. This research approach opens new avenues for improving outcomes in patients with CRC, offering these patients access to immuno-oncological strategies that were previously unavailable to them, Li concludes.