MMR-deficient cancers of any histologic type appear to be very sensitive to PD-1 blockade with pembrolizumab, and similar data are also beginning to emerge for nivolumab and other immune checkpoint inhibitors. Among the MMR-deficient cancers, the best antitumor responses are often associated with high microsatellite instability (MSI-H status), higher tumor mutational burden (TMB), and higher predicted neoantigen load. Prevalence estimates of MMR deficiency across solid tumor types range from 1% to 20% depending on the type of malignancy. In prostate cancer, 1-3% of unselected cases harbor MMR deficiency and/or microsatellite instability. For men who previously received definitive treatment for prostate cancer and subsequently develop detectable prostate specific antigen (PSA) levels, the clinical state is known as biochemically recurrent prostate cancer. The current standard of care treatment for patients with biochemically recurrent prostate cancer is either surveillance or androgen deprivation therapy (ADT). ADT has not been shown to provide a survival benefit in this setting, and the decision to initiate ADT will depend on patient preference and perceived risks of the disease. A non-hormonal therapy such as nivolumab would provide an alternative to ADT in patients with biomarker selected (i.e. dMMR, MSI-H, high TMB, or CDK12-altered) biochemically recurrent prostate cancer.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Nivolumab 480mg intravenously every 4 weeks
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Percentage of Participants With PSA50 Response
Percentage of participants who have received at least 1 dose of Nivolumab who experience a confirmed \>=50% decline in prostate specific antigen (PSA) from baseline, as defined by Prostate Cancer Working Group 3 (PCWG3) criteria.
Time frame: up to 6 months post-intervention, up to 2 years of treatment
PSA Progression-free Survival (PSA-PFS)
Median time from initiation of therapy until confirmed PSA increase of 25% (PCWG3). Estimated using Kaplan-Meier method.
Time frame: From start of treatment until the date of first documented PSA increase of 25%, assessed up to 28 days after last treatment dose.
Number of Participants Who Achieve Undetectable PSA
Number of participants who achieve PSA \< 0.1 ng/mL lasting at least 12 weeks.
Time frame: up to 6 months post-intervention, up to 2 years of treatment
Safety and Tolerability of Nivolumab in Biochemically Recurrent Prostate Cancer as Assessed by Number of Participants Experiencing Treatment-Emergent Adverse Events
Number of participants experiencing adverse events Grade 3 or higher as defined by CTCAE v5.0
Time frame: up to 100 days post-intervention, up to 2 years of treatment
Metastasis-free Survival
Median time from first dose of nivolumab until the development of radiographic metastatic disease on CT imaging and/or bone scan, as defined by PCWG3
Time frame: up to 6 months post-intervention, up to 2 years of treatment
Time to Initiation of Next Systemic Therapy
Median time from first dose of nivolumab until next systemic therapy
Time frame: up to 6 months post-intervention, up to 2 years of treatment
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