Molecular and Genetic Determinants of Response to Carboplatin with or without an ATR Inhibitor (M6620) in mCRPC

Abstract

Alterations in DNA damage repair (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC), and are implicated in responses to carboplatin, PARP inhibitors and immunotherapeutics. Inhibitors of the ATR kinase, which is involved in the DDR response, have been demonstrated to have synergistic activity with platinum compounds in preclinical models. We therefore conducted a Phase 2 study of theATR inhibitor M6620+carboplatin vs. docetaxel+carboplatin in mCRPC (NCI protocol # 10191, NCT03517969). The trial mandates pre-treatment tumor biopsy and research blood collections for circulating cell-free DNA (cfDNA) analyses pre-treatment, every 3 cycles on treatment and at end of study. This proposal is for biomarker studies from these biospecimens and for functional studies in model systems to define genetic correlates of response and resistance to therapy.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2023
Accession Number
AD1196260

Entities

People

  • Atish D. Choudhury
  • Kent W. Mouw

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Biorepositories
  • Bladder Cancer
  • Cancer
  • Castration
  • Cell Line
  • Cells
  • Clinical Trials
  • Computational Science
  • Deep Learning
  • Department Of Defense
  • Diseases
  • Electronic Mail
  • Genomics
  • Medical Personnel
  • Neoplasms
  • Oncology
  • Personnel Management
  • Platinum Compounds
  • Prostate Cancer
  • Students
  • Therapy
  • Whole Genome Sequencing

Readers

  • Oncology
  • Prostate Cancer Biology.

Technology Areas

  • Biotechnology