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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • For Cohort 1, 3 and 4 patients must have failed treatment with at least one PD-1 inhibitor or PD-L1 inhibitor for metastatic MCC - For Cohort 2, patients must not have received any anti-PD-1 or anti-PD-L1 therapy - For Cohort 3, patients must not have received any prior chemotherapy - For Cohort 4, patients must have received at least one prior line of chemotherapy - ECOG performance status of 0 to 1 - Histologically confirmed MCC. Disease must be measurable, with at least 1 measurable lesion by RECIST 1.1 - MCC expressing p53WT based on any CLIA or test approved by local health authority or a validated test (Cohort 1 and 2) - MCC expressing p53WT based Central Lab test (Cohort 3 and 4) - Adequate hematological, hepatic, and renal functions

Exclusion Criteria

  • For Cohort 2, subjects must not have autoimmune disease, medical conditions requiring systemic immunosuppression, prior stem cell transplant, or active infection with HBV or HCV. - Patients previously treated with MDM2 antagonist therapies or p53-directed therapies - History of major organ transplant - Patients with known central nervous system (CNS) metastases that are previously untreated - Grade 2 or higher QTc prolongation (>480 milli-seconds per NCI-CTCAE criteria, version 5.0)

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1, Arm 1 		KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 1, Arm 1b 		KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 1, Arm 2b 		KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 1, Arm 3 		KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 1, Arm 5 		KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 1 Expansion 		KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 2, Arm 1 KRT-232 in combination with avelumab 		KRT-232 will be administered orally, once daily (QD) on Days 1-5, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
  • Drug: Avelumab
    Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
    Other names:
    • Bavencio
Experimental
Cohort 2, Arm 2 KRT-232 in combination with avelumab 		KRT-232 will be administered orally, once daily (QD) on Days 1-7, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
  • Drug: Avelumab
    Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
    Other names:
    • Bavencio
Experimental
Cohort 2 Expansion 		KRT-232 will be administered orally, once daily (QD) per RP2D dose and schedule, in combination with avelumab 800 mg IV on Day 1 and 15 in a 28-day cycle.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
  • Drug: Avelumab
    Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
    Other names:
    • Bavencio
Experimental
Cohort 3 		KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin
Experimental
Cohort 4 		KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
  • Drug: KRT-232
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
    Other names:
    • navtemadlin

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Kartos Therapeutics, Inc.

Study Contact

John Mei
650-542-0136
jmei@kartosthera.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.