With fast-track designation, CN201 is a novel CD19-targeting T-cell-engaging IgG4 bispecific antibody. The Phase I study (NCT05579132) is investigating the safety, tolerability, and preliminary efficacy of CN201 in B-ALL. 

The following data from the dose escalation and expansion of the ongoing study was presented at the ASCO 2024 meeting:

• 7 patients achieved 40 mg and above target doses, 6/7 (85.7%) patients achieved CR/CRi

• Nearly three-quarters of patients had more than 50% blasts in baseline bone marrow

• The MTD was not reached up to 60 mg level

• No immune effector cell-associated neurotoxicity syndrome (ICANS) has been observed so far

• Cytokine release syndrome (CRs) mainly occurred following the first dose. Manageable CRs, No ≥ grade 4 CRs

• Hematological toxicity predominates in grade 3 and above TEAE but its incidence is less than 50%

KOL insights

“CN201 looks promising with good response at higher disease burden and easier admin than Blin. I’m perplexed why no ICANS though because we see some ICANS with Blin even with low disease burden, so I’m wondering whether ICANS will be seen in Ph2 expansion” –Expert Opinion.

“Efficacy with CN201 seems even with high blasts burden. Longest response ongoing at 8 mos. 29% all grade CRS, 3.9% gr3+. No ICANS seen”–Expert Opinion.

Conclusion

Blinatumomab is highly effective at clearing ALL MRD but has less efficacy in patients with high disease burden and requires a 28-day continuous infusion. Less frequent dosing of IV or SC BITES in B-ALL would improve ease of use. CN-201 is a novel CD19/CD3 BITE that contains a humanized IgG4 Fc domain, has a long half-life, and can be dosed IV weekly. In this Phase, I dose escalation study, at a target dose of ≥ 20 mg in patients with moderate to high burden B-ALL, 12/16 achieved CR/CRI (92% MRD-negative).