This trial is testing whether a molecularly targeted chemotherapy drug called abemaciclib and an immunotherapy drug called atezolizumab, alone or in combination, are effective in shrinking or preventing the growth of metastatic prostate cancer. The trial is also testing the safety of the combination of abemaciclib with atezolizumab.
This is a multi-center, open label Phase II study of patients with metastatic castration resistant prostate cancer (mCRPC) who will be treated with abemaciclib and atezolizumab alone or in combination. The U.S. Food and Drug Administration (FDA) has not approved abemaciclib or atezolizumab alone or in combination for use in prostate cancer. Abemaciclib is an orally administered molecularly targeted chemotherapy drug called a cyclin-dependent kinase inhibitor, which acts to block the ability of cancer cells to divide and thus prevents tumors from growing. In the laboratory setting, this drug is effective in prostate cancer models that have become resistant to standard hormonal treatments, and this drug is currently being studied for its effectiveness in prostate cancer in other clinical trials. Atezolizumab is an intravenously administered drug called an immune checkpoint inhibitor, which acts to activate the immune system to kill cancer cells. Atezolizumab is ineffective on its own in most patients with prostate cancer, but is being tested in combination with other drugs for prostate cancer in other clinical trials. Multiple research groups have demonstrated in laboratory model systems that abemaciclib can may make immune checkpoint inhibitors more effective. The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. The study design divides study participants into two separate cohorts. The first cohort is a set of subjects whose tumors are not known to have mutations in the CDK12 gene (the "biomarker unselected cohort") - either because tumor tissue never underwent genetic profiling, or because genetic profiling was performed but did not demonstrate a mutation in the CDK12 gene. In this "biomarker unselected cohort," this study will be testing whether abemaciclib alone or in combination with atezolizumab is an effective treatment strategy. The second cohort of participants is a set of subjects whose tumors are known to have mutations in the CDK12 gene based on genetic profiling of the tumor that occurred prior to enrollment on this study. Prior studies suggest that cancers with mutations in the CDK12 gene can shrink in response to immune checkpoint inhibitors. This study will be testing in study participants whose tumors are known to have mutations in CDK12 whether atezolizumab alone or in combination with abemaciclib is an effective treatment strategy. In addition, the trial is testing the safety of the combination of the two drugs in both cohorts. Participants will receive study treatment for as long as they do not have serious side effects and their disease does not get worse. Participants will be followed after completion of study treatment for up to 24 months It is expected that about 75 people will take part in this research study. Eli Lilly and Company is supporting this research study by providing funding for research and the study drug abemaciclib. Genentech, Inc. is supporting the study by providing the study drug atezolizumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Taken orally 2x daily
Intravenously Day 1 of 21 day cycle
Dana Farber Cancer Institute
Boston, Massachusetts, United States
6-month Progression Free Survival (PFS) Rate
The percentage of participants alive and progression-free at 6 months, as assessed by RECIST 1.1 and PCWG3.
Time frame: 6 months
Objective Response Rate (ORR)
The percentage of evaluable patients who had radiographic response (complete response or partial response) by RECIST 1.1 criteria OR 50% decline in PSA from pretreatment baseline per PCWG3 criteria.
Time frame: 6 months
Number of Participants Experiencing Dose Limiting Toxicity (DLT) in Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized) and CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized) Arms
DLT was assessed by Bayesian Continuous Toxicity Monitoring in Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized) and CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized) arms.
Time frame: DLTs were collected while participants on treatment. Treatment duration up to 18 months.
Clinical Benefit Rate (CBR)
Proportion of evaluable patients who had complete response (CR), partial response (PR) or stable disease (SD) as their best response to treatment in arms biomarker-unselected abemaciclib monotherapy (randomized), biomarker-unselected abemaciclib + atezolizumab (randomized), and CDK12 mutation abemaciclib + atezolizumab (non-randomized)
Time frame: From treatment initiation to end of treatment, with follow-up for up to 2 years after treatment discontinuation
Duration of Response (DOR)
The time from the first documented complete response (CR) or partial response (PR) to the earliest date of disease progression or death, whichever occurs first, as determined by PCWG3 criteria.
Time frame: From the date of first documented CR or PR until disease progression or death, or up to 2 years
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Duration of Therapy (DOT)
The length of time from the first administration of study treatment to the date of treatment discontinuation for any reason
Time frame: From treatment initiation until treatment discontinuation for any reason
Time to Progression (TTP)
The duration of time from the first administration of study treatment to the date of first documented disease progression, as determined by Prostate Cancer Working Group 3 (PCWG3) criteria. Patients without documented progression are censored at the last tumor assessment date.
Time frame: From treatment initiation until documented disease progression, or assessed up to 2 years
12-month Overall Survival (OS)
The percentage of participants who are alive 12 months after the start of treatment
Time frame: 12 months
Number of Participants With Maximum Grade Adverse Events by CTCAE v5.0
Number of participants experiencing adverse events, categorized by the maximum grade according to CTCAE v5.0.
Time frame: From treatment initiation through 100 days after last dose for treatment-emergent adverse events, and up to 2 years after last dose