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736 A phase 1/2 open-label, dose-escalation study of ST-067, a decoy-resistant IL-18 cytokine, given as a monotherapy and with pembrolizumab in advanced solid tumor malignancies
  1. Justin C Moser1,
  2. Ryan Sullivan2,
  3. Matthew H Taylor3,
  4. Igor Puzanov4,
  5. Gerald S Falchook5,
  6. Mario Sznol6,
  7. Virginia E Paton7,
  8. David Chonzi8,
  9. Brage Garofalo9,
  10. Mark Sonnemann9,
  11. Hirdesh Uppal9,
  12. Jeremy Barton10,
  13. Beatrice Y McQueen11,
  14. Aaron M Ring12 and
  15. Harriet Kluger13
  1. 1HonorHealth Research Instittue, Scottsdale, AZ, USA
  2. 2Massachusetts General Hospital, Boston, MA, USA
  3. 3Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA
  4. 4Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
  5. 5Sarah Cannon Research Institute, Denver, CO, USA
  6. 6Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA
  7. 7Simcha Therapeutics, Charlotte, VT, USA
  8. 8Genentech Inc., South San Francisco, CA, USA
  9. 9Simcha Therapeutics, New Haven, CT, USA
  10. 10Consultancy, New Haven, CT, USA
  11. 11Simcha Therapeutics, New Haven, CT, USA
  12. 12Fred Hutchinson Cancer Center, Seattle, WA, USA
  13. 13Yale University, New Haven, CT, 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 IL-18 is an inflammatory cytokine with immuno-stimulatory activities on both the innate and adaptive immune systems. However, tumors generate an IL-18 decoy receptor (IL-18 BP), which inactivates both endogenous and exogenously administered IL-18. A decoy-resistant variant of IL-18 (ST-067) has been developed which binds to IL-18Ra but not IL-18 BP. In murine colorectal and melanoma syngeneic tumor models, ST-067 monotherapy and in combination with an anti-PD1 antibody demonstrated significant tumor regression and prolonged survival with an acceptable safety profile. These preclinical data provide the rationale for the current study which will determine the tolerability of both monotherapy and combination therapy in patients with solid tumor malignancies who have disease progression following the standard of care therapy which will include prior immunotherapy (NCT04787042).

Methods This Phase 1 study is a multi-center, multi-dose dose-escalation trial to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (R2PD) of ST-067 monotherapy and combination therapy with pembrolizumab in subjects with advanced, solid tumor malignancies. Secondary endpoints of the trial include safety, characterization of pharmacokinetics, and immunogenicity. The dose-escalation phase will use a modified toxicity probability interval method to determine R2PD of ST-067 monotherapy and combination therapy with pembrolizumab. All subjects will receive ST-067 by the subcutaneous route once every 7 days. The RP2D for all ST-067 treatment arms will be based on the safety, tolerability, PK, and available preliminary anti-tumor activity. Key eligibility requirements include advanced, pre-treated solid tumor malignancy with adequate end-organ function and a PS of 0–1. All subjects will have pre- and on-treatment tumor biopsies which will be analyzed for PD biomarkers potentially predictive of response to therapy. Subjects will receive treatment until disease progression or unacceptable toxicity. Tumor assessments will be performed every 8 weeks and interpreted according to RECIST v1.1. Recruitment is ongoing in the US.

Acknowledgements Charlotte Halley, Erica Heaton, Lidia Zayas, Ashley Drokin, Tara Foote , Janine Miller, Kayla Pham, Brian Bengyak, Barbara Johnson for study coordination and patient care

Ethics Approval This study was approved by either centralized or local institutional review board committees. All enrolled subjects gave signed informed consent prior to taking part of this study.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the informed consent is available for review by the editor if this journal.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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