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Poster session 01

85P - A circulating, surrogate-systemic biomarker correlates with anti-tumor benefit on LNS8801 therapy

Date

10 Sep 2022

Session

Poster session 01

Topics

Tumour Immunology;  Genetic and Genomic Testing, Counseling;  Immunotherapy

Tumour Site

Melanoma;  Non-Small Cell Lung Cancer;  Carcinoma of Unknown Primary Site (CUP);  Neuroendocrine Tumours;  Colon and Rectal Cancer

Presenters

Justine Cohen

Citation

Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037

Authors

J. Cohen1, C.A. Natale2, J.J. Lin3, P. Lorusso4, A. Mita5, M. Mita6, C.Y. Muller7, M. Orloff8, K.P. Papadopoulos9, J. Rodon10, T.K. Garyantes11

Author affiliations

  • 1 Hematology/medical Oncology, Abramson Cancer Center - University of Pennsylvania, 19104 - Philadelphia/US
  • 2 Research, Linnaeus Therapeutics, 08033 - Haddonfield/US
  • 3 Department Of Medicine, Massachusetts General Hospital and Harvard Medical School, 02114 - Boston/US
  • 4 Medical Oncology, Yale School of Medicine - Radiology and Biomedical Imaging, 06520 - New Haven/US
  • 5 Medicine Department, Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center, 90048 - Los Angeles/US
  • 6 Cancer, Samuel Oschin Comprehensive Cancer Institute Cedars-Sinai Medical Center, 90048 - Los Angeles/US
  • 7 Gynocology, University of New Mexico, 87106 - Albuquerque/US
  • 8 Medical Oncology, Thomas Jefferson Univ Hospital, 19107 - Philadelphia/US
  • 9 Clinical Research Department, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 10 Drug Development Department, The University of Texas M. D. Anderson Cancer Center, 77030 - Houston/US
  • 11 R&d, Linnaeus Therapeutics, 08033 - Haddonfield/US
More

Abstract 85P

Background

LNS8801 is an oral, highly selective agonist of the G protein-coupled estrogen receptor (GPER). LNS8801 normalizes c-Myc levels in cancer cells, inhibits proliferation, suppresses invasion, and enhances immune recognition. LNS8801 is being advanced through clinical trials (NCT04130516) for the treatment of advanced solid tumors. GPER is a widely expressed across tumor types as well as normal tissues, including the pituitary gland. Estrogens are endogenous ligands of GPER, and it is known that exogenous estrogen exposures can induce prolactin secretion that is detectable systemically. GPER signaling is both sufficient and necessary to mediate this effect. Due to circadian rhythms, systemic prolactin levels typically decrease throughout the day. However, we hypothesize that prolactin will increase with LNS8801 treatment.

Methods

Circulating prolactin levels were measured on the first day of treatment in patients with advanced solid tumors. Prolactin levels were measured before dosing LNS8801 and at 0.5, 1, 2, 4, 7 and 10 hours after dosing. Tumor responses were measured every 8 weeks for the 1st year and then every 12 weeks.

Results

In up to 70% of patients treated with LNS8801, systemic prolactin increased over the first 10 hours after treatment. A retrospective analysis correlated this change in prolactin with exposure to LNS8801 and anti-tumor benefit from LNS8801 treatment. The kinetics of plasma prolactin levels immediately follows and tightly trends with LNS8801 plasma exposure. A progression-free survival (PFS) analysis comparing patients with a robust prolactin response to those with a weak/nonresponse was performed. Patients with a robust prolactin response had a statistically significant increase in PFS (p<0.01).

Conclusions

These data suggest that prolactin induction may serve as a surrogate-systemic biomarker of pharmacodynamic engagement of GPER. This biomarker will continue to be assessed in the ongoing clinical studies of LNS8801 for the treatment of cancer. Prolactin induction may be used prior to randomization to identify patients most likely to benefit from LNS8801 therapy in future studies.

Clinical trial identification

NCT04130516.

Editorial acknowledgement

Legal entity responsible for the study

Linnaeus Therapeutics, Inc.

Funding

Linnaeus Therapeutics.

Disclosure

J. Cohen: Non-Financial Interests, Personal, Invited Speaker: Sanofi Genzyme, Regeneron. C.A. Natale: Financial Interests, Personal, Invited Speaker: Linnaeus Therapeutics. M. Orloff: Financial Interests, Personal, Invited Speaker: Immunocore, Ideaya, Delcath; Non-Financial Interests, Personal, Invited Speaker: Trisalus. T.K. Garyantes: Financial Interests, Personal, Invited Speaker: Linnaeus Therapeutics. All other authors have declared no conflicts of interest.

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