This research is studying two experimental drugs, abemaciclib and atezolizumab, alone and in combination with each other, to learn about the safety and effectiveness of these treatments and their side effects. This is an investigational study treatment for adult men with metastatic castrate resistant prostate cancer (mCRPC) who have progressive disease despite previous treatment with androgen deprivation therapy (ADT). One group of men (men without a genetic mutation called "CDK12 loss") will receive abemaciclib therapy alone. Two other groups of men (men with CDK12 loss in one group and men without CDK12 loss in the other) will receive the combination of abemaciclib and atezolizumab. Another group of men with CDK12 loss will receive atezolizumab therapy alone.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
200 MG orally BID Days 1-21
1200 mg IV on Day 1 of 21-day cycle
150 MG orally BID Days 1-21
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Minnesota
Minneapolis, Minnesota, United States
Washington University - St. Louis
St Louis, Missouri, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Progression free survival (PFS) (Arms A and B)
Percentage of patients without disease progression at 6 months after start of treatment. Disease progression as defined by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.
Time frame: 6 months after start of treatment
Incidence of dose limiting toxicities (DLTs) of combination therapy with abemaciclib and atezolizumab
Dose safety for the combination of abemaciclib and atezolizumab is the DLT incidence in Arm B and the combination-therapy cohort of Arm C. DLT is defined in the protocol.
Time frame: From start of treatment to end of cycle 1; up to 21 days
Objective response rate (ORR) (Arms A and B)
The percentage of patients with at least 50% decline in PSA from pretreatment baseline per PCWG3 criteria
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Clinical benefit rate (CBR) (Arms A and B)
CBR as estimated by proportion of evaluable patients who had complete response (CR), partial response (PR) or stable disease (SD) as their best response to treatment by PCWG3 criteria.
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Duration of response (DOR) (Arms A and B)
DOR among responders by PCWG3 criteria will be reported by treatment arm using Kaplan-Meier methods.
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Duration of therapy (DOT) (Arms A and B)
DOT among responders by PCWG3 criteria will be reported by treatment arm using Kaplan-Meier methods.
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Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Time to progression (TTP) (Arms A and B)
TTP among responders by PCWG3 criteria will be reported by treatment arm using Kaplan-Meier methods.
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Number and severity of Adverse Events of Special Interest (AESI) (all arms)
Assessed by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Results will be submitted in tabular format, showing the number of each AESI by grade (names of AESI in rows; grades 1 - 5 in columns). AESIs are protocol-specific (as defined in the protocol).
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Overall survival among all patients (Arms A and B)
Number of patients (in arms A and B) alive at 2 years after the end of their treatment.
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest
Overall survival among patients who respond to treatment (Arms A and B)
Number of patients who responded to treatment (per PCWG3 criteria) alive at 2 years after the end of their treatment.
Time frame: Up to 2 years after end of treatment or until study closes, whichever is earliest