Immunotherapy in Patients With Metastatic Cancers and CDK12 Mutations

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