Clinical Trials /

Pembrolizumab and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer

NCT03406858

Description:

This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. HER2Bi-armed activated T cells are made using T cells and may target and kill cancer cells. Giving pembrolizumab and HER2Bi-armed activated T cells may work better in treating patients with castration resistant prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and HER2Bi-Armed Activated T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer
  • Official Title: Phase II Trial of Immune Checkpoint Inhibitor With Anti-CD3 x Anti-HER2 Bispecific Antibody Armed Activated T Cells in Metastatic Castrate Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2015-135
  • SECONDARY ID: NCI-2017-02156
  • SECONDARY ID: 2015-135
  • SECONDARY ID: P30CA022453
  • NCT ID: NCT03406858

Conditions

  • Castration Levels of Testosterone
  • Castration-Resistant Prostate Carcinoma
  • Prostate Carcinoma Metastatic in the Bone
  • PSA Progression
  • Stage IV Prostate Adenocarcinoma AJCC v7

Interventions

DrugSynonymsArms
HER2Bi-Armed Activated T CellsAnti-CD3 x Anti-Her2/neu Bispecific Antibody-Armed Activated T Cells, HER2Bi-Armed ATCsTreatment (pembrolizumab, HER2Bi-armed activated T cells)
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab, HER2Bi-armed activated T cells)

Purpose

This phase II trial studies how well pembrolizumab and HER2Bi-armed activated T cells work in treating patients with castration resistant prostate cancer that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. HER2Bi-armed activated T cells are made using T cells and may target and kill cancer cells. Giving pembrolizumab and HER2Bi-armed activated T cells may work better in treating patients with castration resistant prostate cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the clinical efficacy of 8 infusions of HER2 HER2Bi-armed activated T cells
      (BATs) (up to 10^10/infusion) twice per week for 4 weeks in combination with pembrolizumab
      once every 3 weeks starting with one dose 3 weeks before the 1st BATs infusion, by assessing
      the percentage of patients free of clinical progression at 6 months after registration.

      SECONDARY OBJECTIVES:

      I. Evaluate phenotype, cytokine profiles and IFN-gamma enzyme-linked immunosorbent spots
      (ELISpots), cytotoxicity and antibodies directed at laboratory prostate cancer cell lines for
      proof of principle of immune system activation and to correlate with clinical outcomes of
      response, progression free survival (PFS), and overall survival (OS).

      II. Evaluate the magnitude of change in tumor infiltrating T cells, PD-1 expression, and the
      Th1/Th2 ratio in prostate cancer tumor tissue before and after immunotherapy and correlate it
      with the clinical outcomes of response, PFS, and OS.

      OUTLINE:

      Patients receive pembrolizumab intravenously (IV) over 30 minutes every 3 weeks. Treatment
      repeats every 3 weeks for up to 6 months in the absence of disease progression or
      unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive
      HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence
      of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab, HER2Bi-armed activated T cells)ExperimentalPatients receive pembrolizumab IV over 30 minutes every 3 weeks. Treatment repeats every 3 weeks for up to 6 months in the absence of disease progression or unacceptable toxicity. Beginning at least 1 week after pembrolizumab, patients receive HER2Bi-armed activated T cells IV over 5-15 minutes 2 times a week for 4 weeks in the absence of disease progression or unacceptable toxicity.
  • HER2Bi-Armed Activated T Cells
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Have histologically confirmed prostate adenocarcinoma, with metastases

          -  Progression by either PSA, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
             criteria for measurable disease or new areas of metastases on bone scan or symptom
             progression related to prostate cancer despite castrate levels of testosterone; (level
             < 50 ng/ml)

          -  Be agreeable to continue to maintain castrate levels of testosterone

          -  At least 2 weeks should have elapsed since any immunosuppressive therapy

          -  At least 4 weeks since prior chemotherapy for metastatic disease or at least 2 weeks
             since prior androgen targeting agents such as ketoconazole, abiraterone, enzalutamide,
             etc.

          -  Discontinue anti-androgens prior to therapy; at least 6 weeks since last dose of
             bicalutamide or nilutamide and at least 4 weeks from last dose of flutamide

          -  Have normal bone marrow, renal and hepatic function as deemed by the treating
             physician and approved by the clinical principal investigator (PI) Dr. Vaishampayan

          -  Not have concurrent anti-cancer therapy

          -  Not have concurrent immunosuppressive therapy or medical condition likely to cause
             immunosuppression

          -  Have life expectancy > 6 months

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group
             (ECOG)/Zubrod performance scale

          -  Agree to use an adequate method of contraception starting with the first dose of study
             therapy through 120 days after the last dose of study therapy

               -  Note: Abstinence is acceptable if this is the usual lifestyle and preferred
                  contraception for the subject

          -  Within 10 days of treatment initiation: Absolute neutrophil count (ANC) >= 1,500 /mcL

          -  Within 10 days of treatment initiation: Platelets >= 100,000 / mcL

          -  Within 10 days of treatment initiation: Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without
             transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)

          -  Within 10 days of treatment initiation: Serum creatinine =< 1.5 X upper limit of
             normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration
             rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >=
             60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

          -  Within 10 days of treatment initiation: Serum total bilirubin =< 1.5 X ULN OR direct
             bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN

          -  Within 10 days of treatment initiation: Aspartate aminotransferase (AST) (serum
             glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum
             glutamate pyruvate transaminase [SGPT] =< 2.5 X ULN OR =< 5 X ULN for subjects with
             liver metastases

          -  Within 10 days of treatment initiation: Albumin >= 2.5 mg/dL

          -  Within 10 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 partial thromboplastin time (PTT) is within therapeutic range of
             intended use of anticoagulants

          -  Within 10 days of treatment initiation: Activated partial thromboplastin time (aPTT)
             =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is
             within therapeutic range of intended use of anticoagulants

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg
             of prednisone daily or equivalent steroid doses) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of trial treatment

          -  Has a known history of active TB (Bacillus tuberculosis)

          -  Has hypersensitivity to pembrolizumab or any of its excipients

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             day 1 or has not recovered (i.e. =< grade 1 or at baseline) from adverse events due to
             agents administered earlier; Note: Subjects with =<grade 2 neuropathy are an exception
             to this criterion and may qualify for the study

          -  Has received major surgery, subject must have recovered adequately from the toxicity
             and/or complications from the intervention prior to starting therapy

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment; this exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability

          -  Has active autoimmune disease that has required systemic treatment in the 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

          -  Has known history of, or any evidence of active, non-infectious pneumonitis

          -  Has an active infection requiring systemic therapy

          -  Has a history 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 known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g. hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g. hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Has received a live vaccine within 30 days of planned start of study therapy; Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g. Flu-Mist) are live attenuated
             vaccines, and are not allowed

          -  Has history of cardiac or pulmonary impairment either by clinical history or symptoms
             or cardiac ejection fraction < 40%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to 6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Barbara Ann Karmanos Cancer Institute

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