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674 A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy in 3L and in combination with pembrolizumab in 1L recurrent/metastatic HPV16+ head and neck cancer patients
  1. Christine H Chung1,
  2. Douglas Adkins2,
  3. A Dimitrios Colevas3,
  4. Cristina Rodriguez4,
  5. Jong Chul Park5,
  6. Michael K Gibson6,
  7. Ammar Sukari7,
  8. Barbara Burtness8,
  9. Faye Johnson9,
  10. Ricklie Julian10,
  11. Nabil F Saba11,
  12. Francis Worden12,
  13. Lara A Dunn13,
  14. Tanguy Y Seiwert14,
  15. Robert M Jotte15,
  16. Rami Haddad16,
  17. Nashat Gabrail17,
  18. Julie E Bauman18,
  19. Marya Chaney19,
  20. Laura Agensky20,
  21. Apollina Goel20,
  22. Steve Quayle20,
  23. Steven Margossian20,
  24. Matteo Levisetti20 and
  25. Sara Pai21
  1. 1Moffitt Cancer Center, Tampa, FL, USA
  2. 2Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, Saint Louis, MO, USA
  3. 3Stanford University, Stanford, CA, USA
  4. 4University of Washington School of Medicine, Seattle, WA, USA
  5. 5Massachusetts General Hospital, Boston, MA, USA
  6. 6Vanderbilt University Medical Center, Nashville, TN, USA
  7. 7Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA
  8. 8Yale University School of Medicine, New Haven, CT, USA
  9. 9The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  10. 10University of Arizona Cancer Center, Tucson, AZ, USA
  11. 11Winship Cancer Institute of Emory University, Atlanta, GA, USA
  12. 12University of Michigan Health System Comprehensive, Ann Arbor, MI, USA
  13. 13Memorial Sloan Kettering Cancer Center, New York, NY, USA
  14. 14Johns Hopkins, Baltimore, MD, USA
  15. 15Rocky Mountain Cancer Center, Lone Tree, CO, USA
  16. 16Affiliated Oncologists, LLC, Chicago Ridge, IL, USA
  17. 17Gabrail Cancer Center, Canton, OH, USA
  18. 18George Washington University Cancer Center, Washington, DC, USA
  19. 19Merck and Co., Inc, Rahway, NJ, USA
  20. 20Cue Biopharma, Boston, MA, USA
  21. 21Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Immuno-STATs are modular T cell engagers engineered to selectively activate tumor-antigen specific CD8+ T cells via targeted delivery of cytokines. CUE-101, the first Immuno-STAT in clinical trials, is composed of a human leukocyte antigen (HLA) complex, HLA-A*0201, a peptide epitope derived from the HPV16 E7 protein, and 4 molecules of attenuated human interleukin-2 (IL-2) designed to bind, expand, and activate HPV16-specific CD8+ T cells for the treatment of HPV16+ cancers.

Methods CUE-101–01 is an ongoing first-in-human study in HLA-A*0201 patients with HPV16+ recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Escalating doses of CUE-101 monotherapy (0.06 mg/kg to 8 mg/kg) were evaluated in R/M HNSCC refractory to ≥ 1 platinum-based or checkpoint inhibitor therapy and in combination with pembrolizumab (1 mg/kg to 4 mg/kg + 200 mg pembrolizumab) in the first line treatment of PD-L1+ R/M HNSCCs followed by expanded enrollment at the recommended phase 2 dose (RP2D). Therapy was administered every 3 weeks until disease progression or intolerable toxicity. Safety, PK/PD, and antitumor activity were assessed.

Results As of June 22, 2023, 71 patients have been enrolled. Following monotherapy and combination therapy dose escalation, 4 mg/kg of CUE-101 was chosen as the RP2D for both monotherapy and pembrolizumab combination cohorts. Monotherapy RP2D enrollment is complete and combination RP2D enrollment is ongoing. Adverse events have been manageable and are consistent with the CUE-101 mechanism of action and underlying disease. Grade 3 AEs reported include lymphocyte count decreased (11.3%), anemia (7.0%), decreased appetite and infusion-related reaction (4.2%). PD data demonstrate selective expansion of HPV-16 E711–20-specific CD8+ T cells, sustained increase in NK cells with only transient increase in Treg cells. Among 19 evaluable monotherapy RP2D patients, 1 PR and 6 durable SD (SD ≥ 12 weeks) were observed, with mOS of 14 months. Among 16 evaluable RP2D CUE-101 and pembrolizumab combination patients at data cut-off, 1 uCR, 4 PRs, 2 uPR, and 4 durable SDs were observed. Of the 7 patients with objective responses, 5 achieved >99% reduction in HPV16 cfDNA, 4 by week 6, with 2 patients pending analysis at time of data cut-off.

Conclusions CUE-101 demonstrates safety, tolerability and results in clinical benefit. Patients treated with CUE-101 monotherapy in 3L showed a long OS and CUE-101 and pembrolizumab combination resulted in an ORR of 44% with a corresponding decrease in HPV16 cfDNA in the 1L treatment of patients with HPV16+ R/M HNSCC.

Acknowledgements The authors would like to thank all the patients who are participating in this study. The study is sponsored by Cue Biopharma, in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and support from LG Chem, Ltd., Seoul, South Korea.

Trial Registration NCT03978689

Ethics Approval This study was approved by IRBs at all study sites: Advarra Pro00037736, IRB 52744, HRPO# 201905108, DF/HCC IRB# 19–374, WIRB STUDY00008948, IRB 191714, 2019–087, WIRB 2000026098, 2019–0578, WIRB 1908869642, WIRB IRB00112341, IRB 20–073, IRB00255391, IRBMED HUM00165746, US Oncol IRB00001113, WCG IRB00000533.

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