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

NCT07472322 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 2026-0149UWMSN | SMPH | DOM HematologyProtocol Version 3/2/26UW26001
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if ASTX727 can be combined with retifanlimab to treat Merkel cell cancer. It will also learn about the safety of combining these drugs. The main questions it aims to answer are:

• Can the combination shrink cancer and lower the chance of the cancer growing or spreading?
• Is the combination better than standard of care for Merkel cell cancer? Participants will:
• Take oral ASTX727 and retifanlimab through a vein in the arm for about 2 years.
• Visit the clinic once every 2 weeks for checkups and tests

Conditions

Merkel Cell Carcinoma; Merkel Cell Carcinoma, Stage III; Merkel Cell Carcinoma, Stage IV

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects with treatment-emergent adverse events

  Adverse events will be measured using NCI Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Grade 3 or greater non-hematological, grade 4 or greater treatment-emergent AEs, and instances where treatment has to be discontinued will be calculated for this measure.

  Up to 27 months (2 years plus 90 days)

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Up to 4 years

• Disease Control Rate (DCR)

  Up to 4 years

• Progression-free Survival (PFS)

  Up to 4 years

• Overall Survival (OS)

  Up to 4 years

• Duration of Response (DoR)

  Up to 4 years

Study Arms (1)

Merkel cell carcinoma

EXPERIMENTAL

Participants with unresectable Merkel cell carcinoma who progressed on prior PD-1 or PD-L1 inhibitor

Drug: ASTX727 + retifanlimab

Interventions

ASTX727 + retifanlimab DRUG

Participants take oral ASTX727 and receive retifanlimab through a vein

Merkel cell carcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

University of Wisconsin-Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

decitabine and cedazuridine drug combination

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Vincent Ma, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cancer Connect

CONTACT

800-622-8922; clinicaltrials@cancer.wisc.edu

Renae Quale, RN

CONTACT

rmq@medicine.wisc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 16, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031
• Last Updated: July 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Access Criteria: Researchers who are doing biomedical research may apply to the PI for access to blood and tissue (no patient identifiers on tubes or slides). Only de-identified information will be released with the specimens

Locations

US (1)