CUE-102, Cue Biopharma’s second drug product candidate, after CUE-101 is designed to activate and expand tumor-specific T cells that target Wilms’ Tumor 1 (WT1)-expressing cancers. Signal 1 incorporates a WT1 peptide, and Signal 2 consists of the engineered IL-2 variant. CUE -102 is being evaluated in a dose escalation and expansion monotherapy Phase I trial in the US, at a starting dose of 1mg/kg, with an initial focus on gastric, pancreatic, ovarian, and colon cancers. Enrollment in dose escalation (Part A) is complete. Patients received 1-8 mg/kg CUE-102 IV every 3 weeks. Following the expansion of 2, 4, and 8 mg/kg dose levels, 4 mg/kg was selected for dose expansion (Part B). Following initial dose expansion in colorectal patients, enrollment is now ongoing for all disease-specific cohorts.

Data from the same was presented at the ASCO 2024 annual meeting which was as follows: 

• CUE-102 was safe and exhibited a manageable tolerability profile with >85.6% AEs being Common Terminology Criteria for Adverse Events (CTCAE) Grade 1-2, no dose-limiting toxicities, and no related SAES. 

• Two patients, one with gastric cancer and one with ovarian cancer demonstrated a reduction in tumor burden. 

• Disease control rate (DCR) in Part A = 43.5%. Of the 28 patients treated in Part A, 13 are alive in survival follow-up. 

KOL insights

“CUE-102 has the potential to activate the patient’s immune system against numerous WT1-expressing cancers, including solid tumors and hematologic malignancies, and has demonstrated selective and significant activation of WT1-specific T cells in preclinical studies” – Expert Opinion.

Conclusion

To conclude, preliminary pharmacokinetics (PK) and pharmacodynamics (PD) analyses demonstrated approximately dose-proportional exposure and evidence of selective stimulation and expansion of WT1-specific CD8 T cells. CUE-102 has the potential to significantly alter the treatment landscape for patients with WT1-positive cancers by offering higher efficacy and lower toxicity compared to currently available treatments. The tolerability profile of CUE-102 together with preliminary evidence of selective immune stimulation supports additional testing of CUE-102 in combination regimens in the future.