Dr Li on the Use of ADG126 With 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 results of a phase 1b/2 study (NCT05405595) utilizing ADG126 in combination with pembrolizumab (Keytruda) in patients with metastatic microsatellite stable (MSS) colorectal cancer (CRC).

The dose-escalation portion of the study found that ADG126 plus pembrolizumab at doses ranging from 6 mg/kg every 3 weeks up to the maximally administered dose of 10 mg/kg once every 3 weeks, is well-tolerated with. Moreover, the regimen was associated with a limited incidence of grade 3 treatment-related adverse effects (TRAEs), similar to that of pembrolizumab monotherapy. This dosing regimen maintained a favorable safety profile and exhibited anti-tumor activity. Notably, the MSS CRC cohort meets the threshold set for part 1 of the Simon’s 2-stage design, with the second stage enrolling currently.

The primary objective of the study was safety and tolerability, followed by additional reporting on efficacy outcomes, particularly for patients with MSS CRC, Li states. During dose escalation, investigators observed that dosing was safe, allowing relatively quick escalation to high doses for anti–CTLA-4 antibodies compared with traditional dosing for similar agents in the field, he explains. The safety analysis revealed that 3 TRAEs in the overall cohort led to study discontinuation, for a 6.5% discontinuation rate.

Despite being administered at high doses, the treatment was well-tolerated, indicating its potential for further dose escalation. Regarding efficacy, investigators noted a 22% ORR in the expansion cohort for MSS CRC without liver metastasis, he emphasizes. Notably, a median PFS of approximately 7 months was observed in a subset of patients without liver or perineal metastasis. This exceeds traditional expectations for PFS in this population, suggesting the need for further investigation, Li concludes.

Overall, this combination significantly widened the therapeutic index compared to similar class agents combined with anti-PD-1 therapy, showing promising early outcomes in MSS CRC patients without liver metastasis.