Merkel Cell Carcinoma, Merkel Cell Carcinoma, Stage III, Merkel Cell Carcinoma, Stage IV
Conditions
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
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.
Interventions
DRUGASTX727 + retifanlimab
Participants take oral ASTX727 and receive retifanlimab through a vein
Sponsors
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of subjects with treatment-emergent adverse events | Up to 27 months (2 years plus 90 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to 4 years | 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). |
| Disease Control Rate (DCR) | Up to 4 years | DCR is defined as the proportion of all subjects with RECIST-based PR, CR, and SD divided by the total number of evaluable participants. |
| Progression-free Survival (PFS) | Up to 4 years | 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 |
| Overall Survival (OS) | Up to 4 years | 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. |
| Duration of Response (DoR) | Up to 4 years | 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. |
| Percentage of participants with tumor reduction | Up to 4 years | At least a 30% decrease in the sum of the diameters of target lesions by RECIST v1.1. |
Countries
United States
Contacts
CONTACTCancer Connect
CONTACTRenae Quale, RN
PRINCIPAL_INVESTIGATORVincent Ma, MD
University of Wisconsin, Madison
Outcome results
None listed