Avelumab Plus 2nd-generation ADT in African American Subjects With mCRPC
Condition: Metastatic Castration-resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Avelumab; 2nd generation ADT (abiraterone or enzalutamide)
Intervention description: Avelumab 10mg/kg every 2 weeks (Q2W) + 2nd generation ADT; 2nd generation ADT (abiraterone or enzalutamide)
Intervention MeSH terms: Avelumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a nonrandomized, open-label trial of avelumab in subjects with metastatic
      castration-resistant prostate cancer (mCRPC) experiencing PSA or radiographic progression
      while receiving 2nd generation ADT (abiraterone / enzalutamide/ apalutamide or darolutamide).
      Metastases must be radiographically evident by whole body bone scintigraphy or CT/MRI scan.

      Thirteen African American subjects will be enrolled into the initial cohort.

      If at least one positive response (PSA decrease by >50% and or radiographic per RECIST 1.1)
      is found, the study will be expanded to accrue a total of 27 patients. The trial will be
      conducted in accordance with Good Clinical Practices.

      Subjects enrolled in the study will receive avelumab 10 mg/kg every 2 weeks (Q2W) and
      continue their previously started 2nd generation ADT (abiraterone or enzalutamide).

      Treatment with avelumab will continue until documented confirmed disease progression,
      unacceptable AEs, intercurrent illness that prevents further administration of treatment,
      Investigator's decision to withdraw the subject, subject discontinuation from the study,
      noncompliance with trial treatment or procedure requirements, subject receives 52
      administrations of avelumab (approximately 2 years), or administrative reasons requiring the
      cessation of treatment.

      After the end of treatment, each subject will be followed for 30 days for AE monitoring
      (serious AEs will be collected for 90 days after the end of treatment or 30 days after the
      end of treatment if the subject initiates new anticancer therapy, whichever is earlier).
      Subjects who discontinue treatment for reasons other than disease progression will remain on
      study and continue to undergo study-related disease assessments until documented disease
      progression, initiation of a new non-study prostate cancer treatment, withdrawal of consent,
      or becoming lost to follow-up. All subjects will enter survival follow up, and will be
      contacted at their regularly scheduled clinic visit, or by telephone approximately every 6
      months, until death or withdrawal of consent or end of study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Must be of African descent; Black or African American: A person having origins in any
             of the black racial groups of Africa. Terms such as "Haitian" or "Negro" can be used
             in addition to "Black or African American."

          2. Be willing and able to provide written informed consent for the trial.

          3. Be ≥18 years of age on day of signing informed consent.

          4. Have histologically or cytologically confirmed adenocarcinoma of the prostate without
             small cell histology. Diagnosis must be stated in a pathology report.

          5. Have evidence of metastatic disease as determined by CT/MRI scans and/or bone
             metastases by whole body bone scintigraphy. (Use MRI if CT is contraindicated, and for
             imaging of the brain if clinically indicated).

          6. Have documented disease progression within 3 months of screening, as determined by the
             Investigator, by means of at least one of the following:

             PSA progression as defined by a minimum of two rising PSA levels with an interval of ≥
             1 week between each assessment where the PSA value at screening should be ≥ 2 ng/mL.

             Radiographic disease progression in soft tissue or bone with or without PSA
             progression as determined by Recist 1.1 and/or PCWG3

          7. Have ongoing androgen deprivation with serum testosterone < 50 ng/dL (< 2.0 nM). If
             the subject is currently being treated with Luteinising Hormone Releasing Hormone
             (LHRH) agonists or antagonists (for subjects who have not undergone an orchiectomy).
             This treatment must be continued throughout the study.

          8. Be receiving and tolerating either abiraterone acetate, enzalutamide, apalutamide or
             darolutamide for at least 8 weeks prior to documented disease progression. Note: the
             2nd generation ADT that the patient is currently progression on needs to be the first
             2nd gen ADT used in the CRPC setting

          9. Have a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group
             (ECOG) Performance Scale (Appendix D).

         10. Male subjects of reproductive potential must agree practice abstinence from
             heterosexual activity OR use a highly effective method of contraception, starting at
             the time of informed consent and continue through 60 days after the last dose of study
             therapy (see section 6.1.1.)

         11. Demonstrate adequate organ function as defined in Table 1, all screening labs should
             be performed within 10 days of treatment initiation.

        Exclusion Criteria:

          1. Is currently participating and receiving study therapy in a clinical trial, or has
             participated in a study of an investigational agent (and received study therapy or
             used an investigation device) within 4 weeks of the first dose of study treatment.

          2. No more than one line of a 2nd generation ADT (abiraterone acetate /enzalutamide/
             apalutamide/darolutamide) for mCRPC is permitted for study entry.

          3. 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.

             Note: the following are allowed: a. intranasal, inhaled, topical steroids, or local
             steroid injection (e.g., intraarticular injection); b. systemic corticosteroids at
             physiological doses < 10mg/day of prednisone or equivalent; c. steroids as
             premedication for hypersensitivity reactions (e.g., CT scan premedication).

          4. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the
             first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to mAbs administered more than 4 weeks earlier.

          5. Has had >2 prior systemic chemotherapy agents for mCRPC Note: chemotherapy in the
             metastatic hormone sensitive prostate cancer (mHSPC) setting is allowed

          6. Prior surgery within 4 weeks of initiating study treatment Note: If subjects received
             major surgery, they must have recovered adequately from the toxicity and/or
             complications from the intervention prior to the first dose of trial treatment.

          7. Has any additional malignancy that has required active treatment in the last 3 years.

             Exceptions include: basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or low-grade Ta or T1 urothelial carcinoma of that bladder that has undergone
             potentially curative therapy.

          8. Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

             Note: 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. This exception does
             not include carcinomatous meningitis which is excluded regardless of clinical
             stability.

          9. Has an active autoimmune disease that might deteriorate when receiving an
             immune-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo-
             or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.

         10. Has had prior organ transplantation including allogenic stem-cell transplantation.

         11. Has an active infection requiring systemic therapy.

         12. Has active, clinically significant Human Immunodeficiency Virus (HIV) (HIV 1/2
             antibodies). Patients with well controlled HIV will be allowed to be enrolled into the
             study.

         13. Has Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
             (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is
             positive).

         14. Has received a live vaccine within 4 weeks of first dose of avelumab; live vaccines
             are prohibited throughout course of the trial. Inactivated vaccines are allowed.

         15. Has known prior severe hypersensitivity to investigational product or component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v4.3 Grade > 3).

         16. Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6months prior to enrollment), myocardial infarction (< 6months
             prior to enrollment), unstable angina, congestive heart failure (> New York Heart
             Association Classification Class II), or serious cardiac ventricular arrhythmia
             requiring medication.

         17. Persisting toxicity related to prior therapy (NCI CTCAE v. 4.3 Grade > 1); however,
             alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety
             risk based on investigator's judgment are acceptable.

         18. Other severe acute or chronic medical conditions including colitis, inflammatory bowel
             disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including
             recent (within the past year) or active suicidal ideation or behavior; or laboratory
             abnormalities that may increase the risk associated with study participation or study
             treatment administration or may interfere with the interpretation of study results
             and, in the judgment of the investigator, would make the patient inappropriate for
             entry into this study.