NCT06056895

Triple Immune Checkpoint Inhibition for Advanced or Metastatic PD-(L)1 Refractory Merkel Cell Carcinoma

A Proof-of-Concept Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Advanced or Metastatic PD-(L)1 Refractory Merkel Cell Carcinoma

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: University of Washington · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well a combination of three immunotherapy drugs work for patients with Merkel cell carcinoma that has spread to lymph nodes and/or distant parts of the body and cannot be treated with surgery (advanced or metastatic MCC) and grew despite prior PD-(L)1 therapy. The three drugs INCMGA00012 (retifanlimab, anti-PD-1), INCAGN02385 (tuparstobart, anti-LAG-3), and INCAGN02390 (verzistobart, anti-TIM-3) are monoclonal antibodies given periodically via IV to reactivate the body's immune system to attack the cancer. This combination may stop tumor growth if tumors have grown despite anti-PD-(L)1 therapy alone.

Detailed description

OUTLINE: All patients receive the same investigational drug combination. SCREENING: Patients undergo history and physical examination, adverse event assessment, safety and eligibility labs, radiologic evaluation with computed tomography (CT)/magnetic resonance imaging (MRI), and complete informed consent. INDUCTION PHASE: Patients receive anti-LAG-3 and anti-TIM-3 intravenously (IV) every 2 weeks along with retifanlimab (anti-PD-1) IV every 4 weeks, along with clinical visit, physical examination, and labs for safety. Treatment continues for up to day 169 in the absence of disease progression or unacceptable toxicity. Patients undergo CT/MRI every 8 weeks. Research tumor biopsies will be obtained on day 1 and day 15 unless unsafe and unfeasible. Research blood draws will occur at day 1, day 15, and periodically throughout Induction Phase. MAINTENANCE PHASE: Patients receive all three drugs IV every 6 weeks along with clinical visit, physical examination, and labs for safety. Treatment continues for up to day 715 in the absence of disease progression or unacceptable toxicity. Patients undergo CT/MRI every 12 weeks. Research blood sample collection will continue periodically. Patients with progressive disease per investigator evaluation will stop receiving therapy. Research blood and tumor biopsies will be obtained at time of progression if safe and feasible. Upon completion of study treatment (day 715 or sooner for disease progression), safety visits occur at 30 and 90 days. Follow up for long term outcomes continues every 6 months for up to 5 years.

Conditions

• Unresectable Clinical Stage III Merkel Cell Carcinoma AJCC v8
• Clinical Stage IV Merkel Cell Carcinoma AJCC v8
• Merkel Cell Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT/MRI
PROCEDURE	Magnetic Resonance Imaging	Undergo CT/MRI
BIOLOGICAL	Retifanlimab	Given IV
DRUG	Tuparstobart	Given IV
DRUG	Verzistobart	Given IV

Timeline

• Start date: 2023-11-08
• Primary completion: 2027-01-31
• Completion: 2027-04-30
• First posted: 2023-09-28
• Last updated: 2026-01-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study