Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma

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

  • Merkel Cell Carcinoma

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