This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with Merkel Cell Carcinoma (MCC) who have failed treatment with at least one anti-PD-1 or anti-PD-L1 immunotherapy or in combination with avelumab in MCC patients who are anti-PD-1 or anti-PD-L1 treatment naïve. Inhibition of MDM2 is a novel mechanism of action in MCC.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
115
Cohort 1 Part 1: To determine the KRT-232 RP2D.
The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm.
Time frame: 10 Weeks
Cohort 1 Part 2: To determine the objective response rate (ORR) in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy
ORR will be assessed per RECIST criteria version 1.1 after all subjects have been treated at the RP2D of KRT 232 and completed the second response assessment.
Time frame: 10 Weeks
Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab
DLTs will be used to establish the MTD of KRT-232 in combination with avelumab. SRC will determine the RP2D based on the safety of combination of KRT-232 with avelumab.
Time frame: 28 Days
Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC
ORR will be assessed per RECIST criteria version 1.1 after all 30 subjects have been treated at the RP2D of in combination with avelumab and have completed the second response assessment.
Time frame: 10 Weeks
Cohort 3: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC are chemotherapy naive and have failed anti-PD-1/PD-L.
ORR will be assessed per RECIST criteria 1.1 by IRC.
Time frame: 10 Weeks
Cohort 4: To determine the confirmed overall response rate (ORR) based on IRC assessments in subjects with p53WT MCC who have failed anti-PD-1 or anti-PDL-1 immunotherapy and have had least 1 line of prior chemotherapy.
ORR will be assessed per RECIST criteria 1.1 by IRC.
Time frame: 10 Weeks
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University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
RECRUITINGMiami Cancer Institute
Miami, Florida, United States
RECRUITINGMoffitt
Tampa, Florida, United States
RECRUITINGNorthwestern Memorial Hospital
Chicago, Illinois, United States
RECRUITINGNorton Healthcare
Louisville, Kentucky, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
RECRUITINGMemorial Sloan-Kettering Cancer Center
New York, New York, United States
RECRUITINGMount Sinai Hospital
New York, New York, United States
RECRUITING...and 41 more locations
To determine the confirmed ORR based on investigator assessment.
ORR will be assessed per RECIST criteria 1.1 by investigators.
Time frame: 1 year after last subject enrolled.
To determine the duration of response (DoR)
Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression.
Time frame: 1 year after last subject enrolled
To determine Progression-free survival (PFS)
Time from initial treatment until disease progression.
Time frame: 1 year after last subject enrolled
To determine overall survival (OS)
Time from initial treatment until death from any cause.
Time frame: 1 year after last subject enrolled
To determine clinical benefit rate (CBR)
PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment.
Time frame: 1 year after last subject enrolled.