IM96, an autologous CAR-T cell therapy, is currently under investigation in an ongoing Phase I dose-escalation study targeting guanylyl cyclase 2C (GC-C). This CAR-T cell therapy aims to assess its safety and effectiveness in patients with colorectal cancer (CRC) who have experienced treatment failure with at least three prior lines of therapy. GC-C, a transmembrane receptor found on the surface of intestinal epithelial cells, remains expressed in both primary tumors and metastatic cells, establishing it as a rational target for cancer therapy.

Out of the nine patients who underwent a single infusion of IM96, 66.7% experienced Grade 1–2 cytokine release syndrome, with a notable increase in interleukin-6 observed in five of these patients. The study administered three different doses of IM96, revealing that any-grade diarrhea and oral mucositis (reported in 55.6% and 33.3% of patients, respectively) were predominantly associated with intermediate and higher IM96 doses (6 × 10⁸ and 12 × 10⁸ CAR-T cells). Importantly, dose-limiting toxicity was not reported.

As per RECIST 1.1 criteria, the study reported a disease control rate of 66.7%, an objective response rate of 11.1%, and observed a reduction in tumor burden in 33.3% of patients. Notably, responders demonstrated enduring tumor remission lasting over 9 months. Among patients exhibiting moderate-to-strong GC-C expression in at least 30% of tumor cells, the disease control rate reached 100%. Furthermore, all patients receiving an IM96 dose equal to or greater than 6 × 10⁸ CAR-T cells experienced a reduction in tumor size. The proliferation of CAR-T cells was evident in all patients, with peak activity occurring between 7 and 14 days post-infusion.

KOL insights

“GC-C appears to be a good target in CRC as it is only expressed in intestinal cells – and over-expressed in cancerous cells – but of course, you also have to think of intestinal side-effects. The frequency of grade 3 diarrhea reported in this study appears acceptable, suggesting that the off-tumor toxicity is not very problematic. However, these are early results in a small number of patients.” – Professor, Denmark.

Conclusion

GC-C emerges as a promising target in colorectal cancer (CRC), given its exclusive expression in intestinal cells and heightened levels in cancerous ones. Despite concerns about potential intestinal side effects, the reported frequency of Grade 3 diarrhea in this study seems manageable, indicating that off-tumor toxicity may not pose a significant issue. It is crucial to note that these findings are based on early results from a limited number of patients. A noteworthy discovery is the traceable proliferation of CAR-T cells post-infusion, indicating their sustained presence without rejection.

For more insight into colorectal cancer, their respective geographical patient burden, treatment, and changing market landscape-related advancements, refer to these reports:

• Colorectal Cancer Market Insight And Market Forecast 
• Metastatic Colorectal Cancer Market Insights And Market Forecast