ASTX727 & Retifanlimab-dlwr for Advanced Merkel Cell After Progression on Anti-PD-(L)1

Inclusion Criteria:

* Individuals age ≥ 18 years at the time of consent
* ECOG Performance Status of 0-2
* Histological or cytological evidence/confirmation of Merkel cell carcinoma (MCC)
* Must have unresectable stage III/IV MCC per American Joint Committee on Cancer (AJCC) 8th edition. Participants must be considered unresectable based on the judgment of the treating physician
* Participants must have progressed on prior programmed cell death protein-1 (PD-1) or programmed death-ligand 1(PD-L1) inhibitor-based therapy. Participants must have received at least 2 doses of anti-PD-1 or anti-PD-L1 inhibitor. Relapsed/refractory disease from prior adjuvant PD-1 or PD-L1 inhibitor is permitted. Prior treatment with retifanlimab is permitted.
* Demonstrate adequate organ and marrow function; all screening labs to be obtained within 28 days prior to registration

Exclusion Criteria:

* Prior treatment with a hypomethylating agent (HMA) (e.g., azacitidine, decitabine, guadecitabine)
* History of clinically significant intolerance, hypersensitivity, or treatment discontinuation of an anti-PD-1 or anti-PD-L1 inhibitor due to grade 3 or greater immune-related adverse events (irAEs). Participants who are able to be successfully rechallenged with anti-PD-(L)1 inhibitor without recurrence of grade 3 or greater irAEs are permitted on study. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study drug(s) may be included (e.g. hearing loss, hypothyroidism, adrenal insufficiency, type 1 diabetes, or other endocrinopathies) after consultation with the sponsor investigator
* Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is \> 30 Gy within 6 months before the first dose of study treatment
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration
* Active infection requiring systemic therapy within 7 days prior to registration