• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

• Age ≥ 18 years at the time of consent.

• Subjects must meet one of the following criteria:

⁃ Subjects suspected or diagnosed with Stage III or IV:

∙ Bladder: Urothelial Carcinoma (UC)

‣ Kidney: Clear Cell Renal Cell Carcinoma (ccRCC)

• Subjects suspected or diagnosed with Stage IV/metastatic:

∙ Colon and Rectum: Microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) Colorectal Cancer (CRC)

‣ Head and Neck: Squamous Cell Carcinoma (HNSCC), excluding nasopharyngeal and salivary gland cancers

‣ Lung: Non-small cell lung cancer (NSCLC)

‣ Skin: Cutaneous Melanoma, excluding Uveal Melanoma

‣ Uterus: endometrial cancer

• Subjects suspected or diagnosed with:

∙ Any metastatic solid tumor with high TMB, MSI-High or dMMR and are being considered for treatment with ICI therapy.

‣ Any metastatic solid tumor that the clinician plans to treat with ICI therapy. NOTE: This can be either in the setting of a trial, compassionate use, or the use of appropriate LDT tests that per clinician, render the patient eligible for ICI therapy, either frontline or a later line.

• Subjects must be clinically able, at investigator discretion, to undergo additional core needle or forceps biopsy passes during their biopsy.

• Subjects who are newly diagnosed or have suspected cancer must be treatment-naïve at the time of biopsy. All other subjects should have the biopsy performed before starting their next line of treatment.

• Subjects with a newly confirmed diagnosis who have previously undergone a standard of care biopsy must be willing to undergo a separate biopsy procedure solely for the purposes of this study.

• Female subjects must not be pregnant.

• Subjects with a known auto-immune disease that would render them ineligible for immune-oncology treatment are not eligible.

• Immunocompromised subjects, and subjects known to be HIV positive and currently receiving antiretroviral therapy are not eligible. NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial.

• Subjects who are enrolled or plan to be enrolled in a blinded oncology treatment trial are not eligible.