Phase II, Open-label, Single-center Study Evaluating Safety and Activity of Androgen Deprivation Therapy Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

Mark Stein1 site in 1 country26 target enrollmentMay 16, 2019

Overview

Brief Summary

The primary objective is to determine the safety and activity of combined hormonal chemoimmunotherapy in a single-arm phase II trial of REGN2810, androgen deprivation therapy (ADT), and docetaxel in patients with newly metastatic, hormone-sensitive prostate cancer (mHSPC), using a primary endpoint of undetectable prostate-specific antigen (PSA) at 6 months, defined from start of combination therapy (week 10) until 6 months (week 37).

Detailed Description

The slow progress for notable trials in metastatic, hormone-sensitive disease is attributed to the long duration of follow-up required, as well as the focus on time-to-event end points, i.e. overall survival, in clinical trial design. These landmark trials (CHAARTED, STAMPEDE, LATITUDE), which used overall survival as their endpoints, required, on average, 10 years from start of trial to first peer-reviewed publication. Given the challenge of using traditional measures of response (RECIST criteria) when designing prostate cancer clinical trials, the Prostate Cancer Working group 2 (PCWG2) made trial-design recommendations. One was to separate treatment outcomes into early measures of response and later time-to-event measures of progression. The goal is to shift the trial objective to capture and reflect the actual effect of the tested treatment and, in doing so, provide a more timely drug development milieu for the metastatic patient. These early measure of response end points, such as undetectable PSA with testosterone recovery, are now being actively integrated into clinical trial design.

Registry

clinicaltrials.gov

Start Date

May 16, 2019

End Date

April 2028

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

Male

Investigators

Sponsor

Mark Stein

Responsible Party

Sponsor Investigator

Principal Investigator

Mark Stein

Associate Clinical Professor of Medical Oncology

Columbia University

Eligibility Criteria

Inclusion Criteria

•Be willing and able to provide written informed consent for the trial.
•Age ≥18 years of age on day of signing informed consent.
•Have life expectancy \> 12 months.
•Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
•Have histologically or cytologically confirmed prostate cancer from prostate biopsy, radical prostatectomy, TURP or from biopsy of a metastatic site. Rarely pathology is not available but if clinical situation confirms prostate cancer (such as prior response to androgen ablation and/or metastatic disease typical of prostate cancer, i.e. involving bone or pelvic/extra pelvic lymph nodes or para-aortic lymph nodes, AND an elevated serum concentration of PSA typical of prostate cancer) pathology is not required and patient can be enrolled after discussed with study PI..
•Have metastatic disease that is either measurable or evaluable (non-measurable).
•Have evaluable (non-measurable) or measurable disease, based on RECIST 1.1, with at least one lesion amenable to biopsy.
•Have testosterone level ≥ 150ng/dL.
•Have not been on androgen deprivation therapy or novel hormonal agents (e.g., abiraterone, enzalutamide, apalutamide) for at least 6 months prior to enrollment in trial and must not have exceeded 24 months of therapy
•Have not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.

Exclusion Criteria

•The subject must be excluded from participating in the trial if the subject:
•Received ADT or other hormonal agents within 6 months prior to entering the study or in the metastatic setting with the exception of 5-alpha reductase inhibitors (e.g.
•finasteride and dutasteride) and first-generation androgen receptor inhibitor (e.g.
•bicalutamide) in setting of normal testosterone. Advise subject to continue the 5-alpha reductase inhibitor for the duration of the study if already started. Advise subject to stop the androgen receptor inhibitor for duration of the study
•Received prior immunotherapy (including inhibitors of programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-CTLA4, or Sipuleucel-T).
•Received prior chemotherapy for prostate cancer treatment.
•Received radiation within 2 weeks prior to entering study.
•Is receiving any other investigational agents concurrently.
•Had a solid organ or hematologic transplant.
•Has active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Arms & Interventions

ADT Followed by Chemoimmunotherapy

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

Intervention: REGN2810

ADT Followed by Chemoimmunotherapy

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

Intervention: Degarelix

ADT Followed by Chemoimmunotherapy

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

Intervention: Leuprolide Acetate

ADT Followed by Chemoimmunotherapy

REGN2810 followed by chemoimmunotherapy: Initiate degarelix 240mg SC once, followed by leuprolide acetate 22.5mg SC every 3 months. Week 4 start cemiplimab (REGN 2810) 350mg IV every 3 weeks (flat dose) for up to 55 weeks or intolerable side effect or progression of disease. Week 10 start docetaxel 75 mg/m2 every 21 days for up to 6 cycles.

Intervention: Docetaxel

Outcomes

Primary Outcomes

Percentage of Subjects Achieving Undetectable PSA at 6 months after Combination Treatment

Time Frame: 6 months

The percentage of subject achieving undetectable PSA levels at 6 months after the combination will use measured to determine safety and activity of combined hormonal chemoimmunotherapy.