| Eligibility |
Inclusion Criteria:
1. Be willing and able to provide written informed consent for the trial.
2. Age =18 years of age on day of signing informed consent.
3. Have life expectancy > 12 months.
4. Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group
(ECOG) Performance Scale.
5. 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..
6. Have metastatic disease that is either measurable or evaluable (non-measurable).
7. Have evaluable (non-measurable) or measurable disease, based on RECIST 1.1, with at
least one lesion amenable to biopsy.
8. Have testosterone level = 150ng/dL.
9. 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
10. Have not received any adjuvant or neoadjuvant chemotherapy or immunotherapy.
11. Have not had prior bilateral surgical orchiectomy.
12. Have not received palliative radiation within 14 days of starting ADT on study
treatment.
13. Have adequate organ and marrow function as defined below:
- Leukocytes =3,000/microliters (mcL)
- Absolute Neutrophil Count =1,500/mcL
- Platelets =100,000
- Hemoglobin = 8.0g/dL (without transfusion in past 2 weeks)
- Prothrombin time (PT)/international normalized ratio (INR), partial
thromboplastin time (PTT) = 1.5 upper limit of normal (ULN) (except if on
therapeutic anticoagulation in which case the patient can be enrolled if stable
and anti-coagulation levels are appropriate for their condition per good clinical
practice).
- Aspartate aminotransferase (AST)(SGOT)/ alanine aminotransferase (ALT)(SGPT) =2.5
× institutional ULN
- Total bilirubin within normal institutional limits. Note: Patients with
hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin
metabolism (e.g. Gilbert's syndrome) will be eligible at the discretion of the
treating physician and/or the principal investigator.
- Creatinine clearance of = 30 mL/min. Creatinine clearance (CrCl) should be
calculated at screening using the Cockcroft-Gault formula.
14. Agree to undergo serial tumor biopsies, unless medically contraindicated in the
opinion of the treating physician, and discussed with the principal investigator
15. The effects of REGN2810 on the developing human fetus are unknown. For this reason and
because REGN2810 agents [as well as other therapeutic agents used in this trial] are
known to be teratogenic, men treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of REGN2810 administration. Should a
woman become pregnant or suspect she is pregnant while her partner is participating in
this study, she should inform her treating physician immediately.
Exclusion Criteria:
The subject must be excluded from participating in the trial if the subject:
1. 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
2. Received prior immunotherapy (including inhibitors of programmed cell death protein 1
(anti-PD-1), anti-PD-L1, anti-CTLA4, or Sipuleucel-T).
3. Received prior chemotherapy for prostate cancer treatment.
4. Received radiation within 2 weeks prior to entering study.
5. Is receiving any other investigational agents concurrently.
6. Had a solid organ or hematologic transplant.
7. 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.
8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.
9. Has a diagnosed malignant disease, other than the tumor type being treated in this
study. Note: Patients with a prior or concurrent malignancy of low metastatic
potential that does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen may be included (e.g., patients with a
history of nonmelanoma skin cancer, carcinoma in situ of the cervix, early stage
cancers treated with curative intent, non-muscle invasive bladder cancer, stage I
renal cancer)Has a known history of, or any evidence of, interstitial lung disease or
active noninfectious pneumonitis.
10. Peripheral neuropathy must be = grade 1
11. Has an active infection requiring systemic therapy.
12. Has a history of current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator, including
dialysis.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). Note:
HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with REGN2810. In addition, these
patients are at increased risk of lethal infections when treated with immunotherapy
and marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.
15. Has untreated active Hepatitis B. Note: To qualify for enrollment, antiviral therapy
for HBV must be given for at least 3 months, and HBV viral load must be less than 100
IU/mL prior to first dose of study drug. Those on active HBV therapy with viral loads
under 100 IU/mL should stay on the same therapy throughout trial treatment. Those
subjects who are anti-HBc (+), and negative for HBsAg, and negative for anti-HBs, and
have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis, but
need close monitoring.
16. Has dual infection with HBV/HCV or other hepatitis combinations at study entry.
17. Has received a live vaccine within 30 days of planned start of study therapy (Cycle 1,
Day 1). Note: The killed virus vaccines used for seasonal influenza vaccines for
injection are allowed; however intranasal influenza vaccines (e.g., FluMist®) are live
attenuated vaccines and are not allowed.
18. Patients with a history of severe hypersensitivity reaction to docetaxel or other
drugs formulated with polysorbate 80 must be excluded.
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