Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations
Condition: Metastatic Castration Resistant Prostate Cancer; Metastatic Cancer; Solid Tumor
MeSH terms: Prostatic Neoplasms; Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary
Intervention: Nivolumab; Ipilimumab
Intervention description: Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.
Patients in arm Metastatic CRPC will receive therapy with monotherapy nivolumab therapy at flat dose 480 mg IV every 4 weeks for up to 104 weeks of total therapy.; Patients in arms Metastatic CRPC and Experimental: Solid Tumors (non-prostate) will begin receiving combination therapy with nivolumab 3 mg/kg IV and ipilimumab 1 mg/kg IV every 3 weeks for up to 4 cycles if tolerated, followed by nivolumab maintenance therapy at flat dose 480 mg IV every 4 weeks through the end of the planned study duration, for up to 104 weeks of total therapy.
Intervention MeSH terms: Nivolumab; Ipilimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Cancer; Metastatic Castration Resistant Prostate Cancer; mCRPC; Immunotherapy; CDK12; Solid Tumor

Summary:

      This study will attempt to determine the efficacy of checkpoint inhibitor immunotherapy with
      nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy in patients
      with metastatic prostate cancer and other tumor solid tumor histologies harboring loss of
      CDK12 function as well as monotherapy nivolumab treatment in patient with metastatic prostate
      cancer harboring loss of CDK12 function.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be ≥18 years of age as of date of signing informed consent.

          -  Be willing and able to provide written informed consent for the study.

          -  ECOG Performance Status of 0, 1 or 2 (Eastern Cooperative Oncology Group scoring
             system used to quantify general well-being and activities of daily life; scores range
             from 0 to 5 where 0 represents perfect health and 5 represents death.

          -  Subjects must have a histologic or cytologic diagnosis of metastatic adenocarcinoma of
             the prostate without small cell histology OR another type of metastatic carcinoma.

          -  All subjects, regardless of cancer type, must have a documented CDK12 aberration in
             tumor tissue.

          -  Subjects with prostate cancer must have documented prostate cancer progression within
             six months prior to screening with PSA progression defined as a minimum of three
             rising PSA levels ≥ 1; 1 week between each assessment with a baseline PSA value at
             screening of ≥ 2 ng/mL.

          -  Subjects with prostate cancer must have ongoing androgen deprivation with total serum
             testosterone < 50 ng/dL (or ≤ 0.50 ng/mL or 1.73 nmol/L)). If the subject is currently
             being treated with LHRH agonists (subjects who have not undergone an orchiectomy),
             this therapy must have been initiated at least 4 weeks prior to registration. This
             treatment must be continued throughout the study.

          -  Subjects with non-prostate histologies must have RECIST 1.1-measurable cancer on
             computed tomography (CT) or magnetic resonance imaging (MRI) scans.

          -  Subjects must have recovered to baseline or ≤ grade 1 toxicities related to any prior
             treatments unless AE(s) are clinically non-significant and/or stable.

          -  Patients must be ≥ 2 weeks from most recent systemic therapy or most recent radiation
             therapy.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             within 28 days prior to registration.

          -  Female and male subjects of reproductive potential must agree to use an adequate
             method of contraception starting with the first dose of study therapy through 5 months
             (for women) and 7 months (for men) after the last dose of study therapy.

          -  Adequate organ and marrow function

        Exclusion Criteria:

          -  Prior treatment with anti-PD-1/PD-L1 and anti-CTLA-4 is NOT allowed. Prior
             intravesical BCG therapy is allowed.

          -  Treatment with any investigational agent or on an interventional clinical trial within
             28 days prior to registration.

          -  Prior or concurrent malignancy except for: adequately treated basal cell or squamous
             cell skin cancer, in situ cervical cancer, localized or locally advanced prostate
             cancer definitively treated without recurrence or with biochemical recurrence only, or
             any other cancer fully treated or from which the subject has been disease-free for at
             least 2 years.

          -  Autoimmune diseases such as rheumatoid arthritis. Vitiligo, mild psoriasis (topical
             therapy only) or hypothyroidism are allowed.

          -  Need for systemic corticosteroids >10mg prednisone daily or equivalent alternative
             steroid (except physiologic dose for adrenal replacement therapy) or other
             immunosuppressive agents (such as cyclosporine or methotrexate) Topical and inhaled
             corticosteroids are allowed if medically needed.

          -  Any history of organ allografts

          -  Any history of HIV, hepatitis B or hepatitis C infection