Clinical Trials Logo

Clinical Trial Summary

This phase II trial compares tuvusertib in combination with avelumab to tuvusertib alone to determine whether the combination therapy will lengthen the time before the cancer starts getting worse in patients with Merkel cell cancer that has not responded to previous treatment (refractory). Tuvusertib is a drug that inhibits an enzyme called ataxia telangiectasia and Rad3 related (ATR) kinase, which is an enzyme that plays a role in repair of damaged deoxyribonucleic acid (DNA) as well as tumor cell replication and survival. It may lead to tumor cell death by inhibiting ATR kinase activity. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tuvusertib in combination with avelumab may lengthen the time before Merkel cell cancer starts getting worse compared to giving avelumab alone.


Clinical Trial Description

PRIMARY OBJECTIVE: I. To compare the potential efficacy, using progression free survival (PFS), of ATR inhibition alone to ATR inhibition plus anti-PD-(L)1 therapy through a randomized clinical trial for patients with advanced Merkel cell carcinoma (MCC) who have progressed on anti-PD(L)1 therapy. SECONDARY OBJECTIVES: I. To compare the clinical activity of ATR inhibition alone to that in combination with avelumab through a randomized clinical trial for patients with advanced MCC that has progressed after PD-1 pathway blockade. II. To identify gene expression-based immunologic (replication stress / neuroendocrine [NE] differentiation) signatures predictive of response to ATR inhibition in advanced immunotherapy-refractory MCC tumors through ribonucleic acid sequencing (RNAseq). EXPLORATORY OBJECTIVES: I. To examine the association of various biomarkers with the clinical activity of ATR inhibition alone or in combination with PD-(L)1 pathway blockade. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive tuvusertib orally (PO) once daily (QD) on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI), biopsy, and collection of blood and stool/rectal swabs at screening and on study. Patients with documented progression may cross over to Arm 2. ARM 2: Patients receive tuvusertib PO QD on days 1-14 of each cycle and avelumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, PET/CT, or MRI, biopsy, and collection of blood and stool at screening and on study. After completion of study treatment, patients are followed up at 30 days and then every 6 months for 2 years. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05947500
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Recruiting
Phase Phase 2
Start date May 21, 2024
Completion date January 1, 2028

See also
  Status Clinical Trial Phase
Recruiting NCT04261855 - Targeted Therapy and Avelumab in Merkel Cell Carcinoma Phase 1/Phase 2
Active, not recruiting NCT03816332 - Tacrolimus, Nivolumab, and Ipilimumab in Treating Kidney Transplant Recipients With Selected Unresectable or Metastatic Cancers Phase 1
Recruiting NCT05269381 - Personalized Neoantigen Peptide-Based Vaccine in Combination With Pembrolizumab for Treatment of Advanced Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT03304639 - Testing the Addition of Radiation Therapy to Immunotherapy for Merkel Cell Carcinoma Phase 2
Active, not recruiting NCT03599713 - A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma (POD1UM-201) Phase 2
Recruiting NCT05896839 - Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer Phase 1/Phase 2
Approved for marketing NCT03089658 - Expanded Access to Avelumab for Treatment of Metastatic Merkel Cell Carcinoma (mMCC)