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2023 Bayer-PCF Darolutamide Challenge Award

Darolutamide to Augment Radiotheranostic Therapy in Biochemically Recurrent Prostate Cancer (DART-BCR)

Principal Investigators: Praful Ravi, MD (Harvard: Dana-Farber Cancer Institute), David Einstein, MD (Beth Israel Deaconess Medical Center)

Young Investigator: Daniel Fein, MD (Beth Israel Deaconess Medical Center)

Co-Investigators: Heather Jacene, MD (Dana-Farber Cancer Institute), Mary-Ellen Taplin, MD (Dana-Farber Cancer Institute), Jacob Berchuck, MD (Dana-Farber Cancer Institute), Steve Balk, MD (Beth Israel Deaconess Medical Center)

Description:

  • The PSMA-targeted radioligand therapy 177Lu-PSMA-617 is approved for use in patients with advanced metastatic castration-resistant prostate cancer (mCRPC), and is now being evaluated in clinical trials in earlier disease settings.
  • Short-term treatment with androgen receptor signaling inhibitors (ARSI) such as darolutamide may increase PSMA expression. This suggests that darolutamide may synergize with PSMA-targeted radioligand therapy and could also increase the sensitivity of PSMA PET imaging for visualizing micro-metastatic tumors.
  • Praful Ravi and team will conduct a novel clinical trial to test the efficacy of darolutamide + 177LuTLX591 (a new PSMA-targeted radioligand therapy) versus darolutamide alone, in patients experiencing a rising PSA after initial therapy, who have at least 1 metastatic lesion detected by PSMA-PET but none by conventional imaging.
  • This trial will also evaluate whether and how darolutamide increases PSMA expression, and whether PSMA PET imaging or other molecular biomarkers can be used to identify patients who are most likely to benefit from the addition of PSMA-targeted radioligand therapy to darolutamide.
  • The impact of this treatment combination on tumor and immune biology will also be investigated.
  • If successful, this project will determine the efficacy of darolutamide alone vs. in combination with PSMA-targeted radioligand therapy in patients at the earliest stages of prostate cancer recurrence after initial treatment. This combination could delay or prevent the onset of metastatic disease and/or the need for long-term anti-androgen therapy.

What this means to patients:  It is possible that improved therapies given at the earliest sign of prostate cancer recurrence after initial surgery or radiation could prevent tumor metastasis and ultimately death from prostate cancer. Dr. Ravi and team will investigate the efficacy of darolutamide alone vs. in combination with PSMA-targeted radioligand therapy in patients experiencing a rising PSA after initial therapy, as well as identify biomarkers for selecting patients most likely to benefit from this therapy combination. This project will also resolve the biology of this treatment and determine how PSMA, the target of prostate cancer treatments and PET imaging, is regulated in prostate cancer, expanding opportunities for new patient treatment and management strategies.