ASCO 2025 | Phase I trial of WTX-212, an erythrocyte-drug conjugate, in advanced cancers
Xiaoqian Nie, PhD, Westlake University, Hangzhou, China, discusses a Phase I trial (NCT06026605) of WTX-212, an erythrocyte-antibody conjugate designed to deliver anti-PD-1 therapy to the spleen in patients with advanced cancers resistant to prior checkpoint inhibitors. WTX-212 was well tolerated, with no dose-limiting toxicities and encouraging signs of anti-tumor activity. Reductions in immunosuppressive myeloid cells correlated with clinical responses, particularly in patients with high baseline levels. This interview took place during the 2025 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
We have developed WTX-212, a first-in-class erythrocyte-based therapy, which is erythrocyte anti-PD-1 antibody conjugates, and I will refer to as PD-1 ARY. So why we use red blood cells or erythrocytes to fight cancers? Because traditionally they were just seen as the carriers of oxygen. But in our study we revealed that they actually can closely interact with our immune system...
We have developed WTX-212, a first-in-class erythrocyte-based therapy, which is erythrocyte anti-PD-1 antibody conjugates, and I will refer to as PD-1 ARY. So why we use red blood cells or erythrocytes to fight cancers? Because traditionally they were just seen as the carriers of oxygen. But in our study we revealed that they actually can closely interact with our immune system. And in fact, they naturally home to the spleen, the largest secondary lymphoid organ, which contains a large amount of tumor-reactive T cells. And by leveraging the splenic homing ability of erythrocytes, PD-1-ARY can precisely target the splenic immune microenvironment and induce significant expansion of effector T cells, as well as the reduction of suppressive myeloid cells. And this change further reprograms the tumor microenvironment and thereby induces strong anti-tumor immunity. And we also launched a first-in-human trial to evaluate the safety, tolerability, and the preliminary efficacy of PD-1-ARY in patients with solid tumors. And all the patients enrolled must have received PD-1 or PD-L1-containing regimen as their last line treatment and then they experienced disease progression and then they will be enrolled for the PD-1-ARY treatment. And so as of now we have enrolled 14 patients across 11 types of solid tumors. And regarding the efficacy, we observed a really encouraging efficacy profile of PD-1-ARY monotherapy in these patients. And the DCR was 78.6 and the ORR was 42.9, including two complete responses and four partial responses. And we also noted that the responses were observed in multiple types of solid tumors, including esophageal cancer, small cell lung cancer, rectal cancer, and urothelial carcinoma indicating the pan-tumor treatment potential of PD-1-ARY. And regarding the safety, PD-1-ARY also enables a favorable safety profile. No DLT or TRAE above grade 3 were observed. We just observed some mild and transient adverse events such as hypertension and fever and all were manageable. And so most importantly, all the patients were able to go home on the same day of transfusion, supporting the feasibility of PD-1-ARY as an outpatient cellular treatment. So that’s a brief overview of our first-in-class red cell-based drug.
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