Inclusion Criteria:

• Age ≥ 18

• Disease-causing, germline FH mutation including variants considered either:

  • a) Pathogenic/likely pathogenic OR
  • b) variants of unknown significance (VUS) with immunohistochemical staining showing loss of FH or high 2-SC expression in tumor tissue

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1

• Thiopurine S-methyltransferase (TPMT) and NUDT15 homozygous, wild-type genotype

  • TPMT*1/TPMT*1 and NUDT15*1/ NUDT15*1

• Calculated creatinine clearance ≥ 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula OR serum creatinine < 1.5 x upper limit of normal (ULN)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN (< 5 x ULN if liver metastases are present)

• Total bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin up to 3.0 mg/dL)

• Albumin ≥ 2.2 mg/dL

• White blood cells (WBC) > 2,000/mm^3

• Hemoglobin (Hb) ≥ 9

• Neutrophils > 1,500/mm^3

• Platelets > 100,000/mm^3

• Inclusion into ≥ 1 of the following symptomatic, disease states listed below:

  • Inclusion allows entry into that cohort for efficacy assessments. Patients can be in ≥ 1 cohort if they have more than one disease manifestation fitting the below criteria. If a patient fits inclusion/exclusion into one cohort and has disease manifestations that are excluded from another cohort, they can still participate in the trial but will not be assessed for efficacy for that specific disease manifestation

• KIDNEY CANCER COHORT: Advanced, metastatic kidney cancer disease

• KIDNEY CANCER COHORT: Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

• KIDNEY CANCER COHORT: ≥ 1 lines of systemic therapy (not considering adjuvant)

• UTERINE FIBROIDS COHORT: Age ≥ 18

• UTERINE FIBROIDS COHORT: Female biologic sex

• UTERINE FIBROIDS COHORT: Any pre-menopausal patient

• UTERINE FIBROIDS COHORT: Fibroid-associated symptoms including symptomatic menorrhagia and/or pelvic pain/pressure

• UTERINE FIBROIDS COHORT: Estimated ≤ 15-week uterus by bimanual exam OR by radiographic parameters (≤ 10 cm max dimension of largest fibroid or estimated weight ≤ 400 g)

• UTERINE FIBROIDS COHORT: Be willing to use non hormonal contraception if needed

• CUTANEOUS LEIOMYOMAS COHORT: ≥ 5 cutaneous leiomyomas

• CUTANEOUS LEIOMYOMAS COHORT: Leiomyoma-associated pain or paresthesia causing weekly pain ≥ 4/10 on a pain scale

Exclusion Criteria:

• Absolute contraindication to the use of contrast-enhanced imaging for efficacy assessment. If moderate allergy, patients could be allowed if pre-medication can be given to limit adverse reactions. (*Not relevant for skin-only cohort)

• Presence of untreated brain metastases. Treated brain metastases must be stable for 4 weeks after treatment, have no clinical symptoms, and not be on corticosteroids > 10 mg/day of prednisone-equivalent > 2 weeks prior to treatment. Patients with known leptomeningeal metastases are excluded

• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications within 14 days prior to first dose of study drug. An exception is allowed for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry

• Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or interfere with the interpretation of safety results

• Individuals who are pregnant; negative serum pregnancy tests in patients of childbearing potential and consent to an effective contraceptive method (if needed Centers for Disease Control and Prevention [CDC] guidelines provided) until a minimum of 30 days after cessation of therapy

• Individuals who wish to continue actively breast-feeding must agree to not breastfeed during the study or for 180 days after the last dose of study treatment

• An untreated non-renal malignancy with the following exceptions:

  • low risk prostate cancer on active surveillance (National Comprehensive Cancer Network [NCCN] very low/low risk)
  • non-melanoma skin cancer

• Any prior treated, non-renal malignancy except for those meeting the following characteristics:

  • Treated stage I or II cancer from which the patient is currently in complete remission
  • Stage III cancer in remission for > 2 years and is not receiving any current treatment
  • A hematologic malignancy from which the patient is considered to be in complete remission

• UTERINE FIBROIDS COHORT: Hormonal management ≤ 2 months of starting treatment. Including gonadotrophin releasing hormone (GnRH) analog, progestins or estrogen (pills or intrauterine devices), or ulipristal acetate

• UTERINE FIBROIDS COHORT: GnRH analog usage ≤ 12 months of starting treatment

• UTERINE FIBROIDS COHORT: History of uterine artery embolization

• UTERINE FIBROIDS COHORT: Prior radiofrequency ablation to a target lesion

• UTERINE FIBROIDS COHORT: History of MR guided focused ultrasound

• UTERINE FIBROIDS COHORT: Myomectomy ≤ 1 year of starting therapy

• UTERINE FIBROIDS COHORT: Concern for gynecologic malignancy

• UTERINE FIBROIDS COHORT: Any Federation of Gynecology and Obstetrics (FIGO) 1 or FIGO 2 myomas requiring immediate treatment

• UTERINE FIBROIDS COHORT: Planning pregnancy in the next 6 months

• UTERINE FIBROIDS COHORT: History of endometrial ablation

• UTERINE FIBROIDS COHORT: Hormonal intrauterine device (IUD) in place

• CUTANEOUS LEIOMYOMAS COHORT: Willingness/ability to have all cutaneous lesions completely removed