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Remarkable response to a novel ATR inhibitor in a patient with poorly differentiated neuroendocrine carcinoma

Yoshihito David Saito1, Zaibo Li2, Maryam Lustberg1

  • 1Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.

Cancer Treatment and Research Communications
|July 13, 2019
PubMed

Insights

M6620, an ATR inhibitor, showed an exceptional response in a patient with metastatic prostate cancer that evolved into neuroendocrine carcinoma. This combination therapy with cisplatin warrants further investigation for advanced cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Ataxia telangiectasia and Rad3-related protein (ATR) is a kinase crucial for DNA damage response and cell cycle arrest.
  • ATR inhibition potentiates the efficacy of DNA-damaging agents and radiation in various cancers.
  • M6620 (VX-970) is a potent ATR inhibitor currently in early-phase clinical trials.

Purpose of the Study:

  • To report an exceptional response in a patient with metastatic prostate cancer that underwent clonal evolution to poorly differentiated large cell neuroendocrine carcinoma.
  • To evaluate the safety, tolerability, and pharmacokinetics of M6620 in combination with cisplatin in a phase I trial (VX12-970-001).

Main Methods:

  • A patient with metastatic prostate cancer and subsequent evolution to neuroendocrine carcinoma was treated with M6620 and cisplatin on a phase I clinical trial.
  • Clinical response, progression-free survival, and safety data were assessed.

Main Results:

  • The patient achieved over 20 months of non-CNS progression-free survival, demonstrating an exceptional response to M6620 and cisplatin.
  • The study provides insights into the mechanism of action of M6620 and its potential in treating advanced malignancies.

Conclusions:

  • M6620 in combination with cisplatin can induce an exceptional and durable response in patients with advanced prostate cancer that has evolved into neuroendocrine carcinoma.
  • This case highlights the potential of ATR inhibitors in overcoming treatment resistance and managing aggressive cancer subtypes.
Keywords:
ATMATRClinical trialDNA damage responseM6620VX-970

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