PRIMARY OBJECTIVES:
I. To determine the safety and tolerability for an established effective dose of systemic
REGN2810 and intraprostatic ipilimumab with stereotactic body radiation therapy (SBRT) in
patients with locally advanced prostate cancer with or without oligometastatic disease.
SECONDARY OBJECTIVES:
I. To determine overall pathologic response rate after radical prostatectomy. II. To
determine prostate-specific antigen (PSA) progression free survival in men treated with
REGN2810 and intraprostatic ipilimumab with SBRT.
III. To determine radiographic progression free survival in men treated with REGN2810 and
intraprostatic ipilimumab with SBRT.
IV. Acute and chronic adverse events (AEs).
Inclusion Criteria:
- Be willing and able to provide written informed consent for the trial
- Have progressive advanced prostate cancer based on at least one of the following
criteria:
- Gleason score of ≥ 7
- Any PSA
- TNM clinical stage T3-T4, N1
- Oligometastatic prostate cancer patients who have not received primary therapy are
eligible; (oligometastatic disease is defined as a patient with ≤ 3 metastatic bone
lesions on the bone scan or tissue metastasis)
- To be scheduled for a Radical Prostatectomy
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
performance scale
- Absolute neutrophil count (ANC) ≥ 1000 /mcL within 7 days of treatment initiation
- Platelets ≥ 150,000 / mcL within 7 days of treatment initiation
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L within 7 days of treatment initiation
- Lymphocytes ≥ 500 / mcL within 7 days of treatment initiation
- Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (CrCl) ≥ 50 mL/min for subject with creatinine levels > 1.5 X
institutional ULN within 7 days of treatment initiation
* Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl
- Serum total bilirubin ≤ 1.5 X ULN within 7 days of treatment initiation
* Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN within 7
days of treatment initiation
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 X
ULN within 7 days of treatment initiation
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or INR is within therapeutic
range of intended use of anticoagulants within 7 days of treatment initiation
- Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless subject is receiving
anticoagulant therapy as long as aPTT is within therapeutic range of intended within 7
days of treatment initiation
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent within 4 weeks of the first dose of treatment
- Prior treatment with an agent that blocks PD-1/PD-L1 pathway or other immune
modulating agents within fewer than 4 weeks of 4 half-lives
- Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or
any form of immunosuppressive therapy within 7 days prior to day 1 of trial treatment
- Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not
recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents
administered more than 4 weeks earlier
- Has had prior treatment with idelalisib
- Has had prior or current treatment with Androgen Deprivation Therapy
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at
baseline) from adverse events due to a previously administered agent
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy
- Note: Subjects with ≤ grade 2 neuropathy are an exception to this criterion and
may qualify for the study
- Has a known additional malignancy that is progressing or requires active treatment;
exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, superficial urothelial cancer, or superficial bladder cancer that has undergone
potentially curative therapy
- Has an active autoimmune disease requiring systemic treatment within the past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs) or a documented history of clinically severe autoimmune disease, or a syndrome
that requires systemic steroids or immunosuppressive agents
- Has evidence of interstitial lung disease, active, non-infectious pneumonitis
- Has evidence of significant liver disease
- Has an active infection requiring systemic therapy; prior to dosing with REGN2810 the
subject must be at least 5 half-lives from their last dose of antibiotic
- Has a history of listeriosis or 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
- Has psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial
- Has a contraindication to administration of amoxicillin, ampicillin, ciprofloxacin,
erythromycin, gentamycin, penicillin, trimethoprim/sulfamethoxazole, and vancomycin
- Is expecting to spontaneously conceive or father children within the projected
duration of the trial, starting with the screening visit through 120 days after the
last dose of trial treatment
- Has contraindication to administration of non-steroidal anti-inflammatory drugs
(NSAIDS)
- Is or has an immediate family member (spouse or children) who is investigational site
or staff directly involved with this trial, unless prospective Institutional Review
Board (IRB) approval (by chair or designee) is given allowing exception to this
criterion for a specific subject
