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

UW26001 Phase I/II Study on the Safety, Tolerability, and Preliminary Efficacy of ASTX727 (Decitabine/Cedazuridine) and Retifanlimab-dlwr in Patients With Advanced Merkel Cell Carcinoma Who Have Progressed on Anti-PD-(L)1 Inhibitor

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

Study Overview

• Status: Not yet recruiting
• Conditions: Merkel Cell Carcinoma; Merkel Cell Carcinoma, Stage III; Merkel Cell Carcinoma, Stage IV
• Intervention / Treatment: Drug: ASTX727 + retifanlimab

Detailed Description

This study is being done to see if combining ASTX727 (decitabine/cedazuridine) with retifanlimab-dlwr is safe and confers clinical benefit in patients with advanced Merkel cell carcinoma who have progressed on anti-PD-(L)1 inhibitor therapy.

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Cancer Connect; Phone Number: 800-622-8922; Email: clinicaltrials@cancer.wisc.edu
• Study Contact Backup: Name: Renae Quale, RN; Email: rmq@medicine.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin-Carbone Cancer Center
      • Contact: Cancer Connect; Phone Number: (800) 622-8922; Email: clinicaltrials@cancer.wisc.edu
      • Contact: Renae Quale, RN; Email: rmq@medicine.wisc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Merkel cell carcinoma; Participants with unresectable Merkel cell carcinoma who progressed on prior PD-1 or PD-L1 inhibitor	Drug: ASTX727 + retifanlimab; Participants take oral ASTX727 and receive retifanlimab through a vein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the proportion of subjects who have a partial response [PR] or complete response [CR] per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (1.1).	Up to 4 years
Disease Control Rate (DCR)	DCR is defined as the proportion of all subjects with RECIST-based PR, CR, and SD divided by the total number of evaluable participants.	Up to 4 years
Progression-free Survival (PFS)	PFS is defined as the interval from start of treatment to first documentation of disease progression per RECIST 1.1 or death from any cause. Participants who have not progressed will be right-censored at the date of the last disease evaluation	Up to 4 years
Overall Survival (OS)	OS is defined as the interval from start of treatment to death of any cause. Participants alive at last time of contact will be right-censored.	Up to 4 years
Duration of Response (DoR)	DoR is defined as the time from documentation of response (PR, CR) to treatment to the first documentation of tumor progression per RECIST 1.1 or death due to any cause, whichever comes first.	Up to 4 years
Percentage of participants with tumor reduction	At least a 30% decrease in the sum of the diameters of target lesions by RECIST v1.1.	Up to 4 years

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Vincent Ma, MD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 1, 2031
• Study Completion (Estimated): May 1, 2031

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Infections; Virus Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; DNA Virus Infections; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Tumor Virus Infections; Polyomavirus Infections; Carcinoma, Neuroendocrine; Carcinoma, Merkel Cell; decitabine and cedazuridine drug combination
• Other Study ID Numbers: 2026-0149; UWMSN | SMPH | DOM Hematology (Other Identifier: UW Madison); Protocol Version 3/2/26 (Other Identifier: UW Madison); UW26001 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Researchers must have local IRB approval for their study that is to include study of the biospecimens and accompanying data. Release of biospecimens to non-UW researchers will be performed according to all UW regulatory policies. Tissue (including blood) specimen as part of this research will be primarily stored at UW and may be sent to an outside lab/facility to achieve the objectives of the study. No study data or patient health information will be shared with a third party.
• IPD Sharing 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
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No