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482 Phase1/2 study of an anti-galectin-9 antibody, LYT-200, in patients with metastatic solid tumors
  1. Aleksandra Filipovic1,
  2. Zev Wainber2,
  3. Judy Wang3,
  4. Johanna Bendell4,
  5. Filip Janku5,
  6. Manish Sharma6,
  7. Amit Mahipal7,
  8. Joseph Bolen1,
  9. Eric Elenko1,
  10. Christopher Korth1 and
  11. George Dranitsaris8
  1. 1Puretech Health, Boston, MA, USA
  2. 2UCLA School of Medicine, Los Angeles, CA, USA
  3. 3Florida Cancer Specialists/SCRI, Sarasota, FL, USA
  4. 4Sarah Cannon Research Institute, Nashville, TN, USA
  5. 5MD Anderson Cancer Center, Houston, TX, USA
  6. 6START Midwest, Grand Rapids, MI, USA
  7. 7Mayo Clinic, Rochester, MN, USA
  8. 8Falk College, Syracuse University, Syracuse, NY, USA


Background Galectin-9 (gal-9) acts as a pivotal immuno-suppressor that disables immune mediated activity through modulation of T cells, macrophages and other immune functions. As such it has emerged as a powerful biological target for cancer immunotherapy and a potential biomarker of response and/or prognosis. Patients exhibiting high gal-9 expression in tumors and blood often have poor prognosis and tumors with aggressive and immunosuppressed molecular features (Chen L. et al, AACR 2020-LB-350). LYT-200 is a fully human IgG4 monoclonal antibody targeting gal-9. LYT-200 has high affinity, high specificity, stability, and blocks galectin-9 interactions with its binding partners in biochemical and human cell-based assays. In murine models of melanoma and pancreatic cancer, LYT-200 significantly reduced tumor growth, extended survival and modulated the intra-tumoral immune microenvironment. LYT-200 treated patient derived tumor organoids showed an increase in T cell activation (Chen L. et al, SITC 2019-P765).

Methods LYT-200 is now being evaluated in the USA, in the first part of an adaptive Phase 1/2 trial (NCT04666688) in relapsed/refractory solid tumors. Patients with solid tumor malignancy that is metastatic or unresectable and refractory to prior therapy are included. Patients are treated with LYT-200 by IV infusion, every 2 weeks (Q2W), until disease progression or toxicity. Phase 1 of the study uses the continuous reassessment design (CRM), and entails recruiting two patients per dosing level. Starting dose level was 0.2mg/kg Q2W. Additionally, the protocol stipulates six patients must be treated at the dose level intended to be declared recommended phase 2 dose (RP2D), for more robust assessment of safety/tolerability. RP2D may be the maximum tolerated dose or the optimal biological dose. The primary objective of the ongoing Phase 1 is to assess the safety and tolerability of LYT-200 and to identify the RP2D. The Phase 1 is also assessing LYT-200’s pharmacokinetics, immunogenicity and pharmacodynamics (measuring circulating gal-9 and cytokine levels, immunophenotyping peripheral blood mononuclear cells and tumor tissue). Preliminary efficacy is captured as an exploratory endpoint in Phase 1. Phase 2 expansion cohorts would implement the Simon’s two-stage design to further assess LYT-200 as a single agent and/or in combination with chemotherapy and tislelizumab. Phase 2 is currently planned in pancreatic cancer and other/different tumor types for Phase 2 may be guided by results of the Phase 1.

Acknowledgements All clinical trial sites participating in the LYT-200 study. Shohei Koide, Linxiao Chen and George Miller and their teams at New York University Langone Health & New York University School of Medicine, NY for all the preclinical work on LYT-200.

Trial Registration NCT04666688

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