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636 A phase 1, open-label, dose escalation and expansion study of CUE-102 monotherapy in HLA-A*0201 positive patients with WT1-positive recurrent/metastatic cancers
  1. Steven Margossian1,
  2. John Powderly2,
  3. Nashat Gabrail3,
  4. Yvonne Saenger4,
  5. J Eva Selfridge5,
  6. Nataliya Uboha6,
  7. Jun Gong7,
  8. Brian Van Tine8,
  9. Olatunji Alese9,
  10. Dae Won Kim10,
  11. Wen Ma11,
  12. Tanios Bekaii-Saab11,
  13. Jeremy Jones11,
  14. Angela Alistar12,
  15. Laura Agensky1,
  16. Apollina Goel1,
  17. Reena Lynam1,
  18. Raymond Moniz1,
  19. Steve Quayle1,
  20. Cynthia Rajan1,
  21. Kenneth Pienta15 and
  22. Matteo Levisetti1
  1. 1Cue Biopharma Inc., Boston, MA, USA
  2. 2Carolina BioOncology, Huntersville, NC, USA
  3. 3Gabrail Cancer Center, Canton, OH, USA
  4. 4Albert Einstein Cancer Center, Bronx, NY, USA
  5. 5UH Cleveland, Cleveland, OH, USA
  6. 6Carbone Cancer Center, Madison, WI, USA
  7. 7Cedar Sinai, Los Angeles, CA, USA
  8. 8Washington University, St Louis, MO, USA
  9. 9Emory University, Atlanta, GA, USA
  10. 10H. Lee Moffitt Cancer Center, Tampa, FL, USA
  11. 11Mayo Clinic, Rochester, MN, USA
  12. 12Carol G. Simon Cancer Center, Winston Salem, NJ, USA
  13. 15Johns Hopkins University School of Med, Cambridge, MD, USA


Background Immuno-STATsTM are modular fusion proteins designed for the selective activation of tumor-antigen specific CD8+ T cells. CUE-102, the second Immuno-STAT in clinical trials, is composed of a human leukocyte antigen (HLA) complex, HLA-A*0201, a peptide epitope derived from the Wilms Tumor 1 (WT1) protein, and 4 molecules of reduced affinity human interleukin-2 (IL-2), and is designed to bind, expand, and activate WT1-specific CD8+ T cells for the treatment of WT1-positive cancers. In pre-clinical studies, CUE-102 elicits selective expansion of WT1-specific cytotoxic CD8+ T-cells in vitro and in vivo.1

Methods CUE-102-01 is a phase 1, open-label, 2-part, multi-center study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of CUE-102 monotherapy administered every three weeks in HLA-A*0201 positive patients with WT1 positive recurrent/metastatic Colorectal, Gastric/Gastroesophageal Junction (GEJ), Pancreatic and Ovarian cancer who have failed conventional therapies. Part A is a dose escalation phase following 3+3 design rules with a Bayesian Logistic Regression Model (BLRM) overlay. Dose levels that exhibit an immune response may be expanded to further characterize activity and toxicity. Part B is a dose expansion/confirmation phase in patients with colorectal cancer.

The primary objectives of Part A are to evaluate dose-limiting toxicities and maximum tolerated dose during the first cycle of treatment, to evaluate the pharmacokinetics (PK) of CUE-102, and to establish a recommended Phase 2 dose. Secondary objectives of Parts A and B include evaluating the safety and tolerability of CUE-102 using NCI CTCAE v5.0; preliminary antitumor activity by RECIST 1.1 including objective response rate (ORR), duration of response (DOR), durable stable disease (DSD) (SD ≥ 6 weeks), clinical benefit rate (CBR), progression-free survival (PFS); overall survival (OS); the potential for CUE-102 mediated immune response; and the potential immunogenicity of CUE-102. Exploratory objectives include evaluation of biomarkers of activity and immune effects, and preliminary antitumor activity by iRECIST.

Eligible patients must have locally advanced/nonresectable or metastatic disease, an ECOG status of 0 or 1, life expectancy > 12 weeks and measurable disease by RECIST 1.1 criteria. Patients with colorectal and cisplatin-sensitive ovarian cancer must have documented disease progression to 2 prior systemic treatment regimens (CUE-102 will be ≥ 3rd line therapy); patients with Gastric/GEJ, pancreatic and cisplatin-resistant ovarian cancer must have documented disease progression to 1 prior systemic treatment regimens (CUE-102 will be ≥ 2nd line therapy).

Results Trial is currently open and enrolling as of June 14, 2022.

Acknowledgements The authors would like to thank all the patients who are participating in this study. The study is sponsored by Cue Biopharma.

Trial Registration ClinicalTrials. gov NCT05360680


  1. Zhang C, Girgis N, Merazga Z. et al. CUE-102 selectively activates and expands WT1-specific T cells for the treatment of patients with WT1+ malignancies. JITC. 2021;9(Suppl 3):A749–A749

Ethics Approval This study was approved by Ethics and Institutional Review Boards (IRBs) at all study sites. IRB reference numbers: WIRB 1331836 (Carolina BioOncology), WIRB 1335388 (Gabrail Cancer Center)

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