Recruiting
Phase 1
Phase 2

Navtemadlin with Anti-PD-1/Anti-PD-L1

Sponsor:

Kartos Therapeutics, Inc.

Code:

NCT03787602

Conditions

Merkel Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

KRT-232

Avelumab

Study Details

Brief summary:

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.

Conditions

Merkel Cell Carcinoma

Study ID

NCT03787602

Start date

Mar 19, 2019

Status verified date

Feb, 2023

Completion date

Aug, 2025

Anticipated

Primary completion date

Nov, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Enrollment

115 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1, Arm 1

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.

experimental: Cohort 1, Arm 1b

KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.

experimental: Cohort 1, Arm 2b

KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.

experimental: Cohort 1, Arm 3

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.

experimental: Cohort 1, Arm 5

KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.

experimental: Cohort 1 Expansion

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

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.

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.

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.

experimental: Cohort 3

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

experimental: Cohort 4

KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.

Interventions

KRT-232

KRT-232 is an experimental MDM2 anticancer drug taken by mouth.

Avelumab

Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.

Primary outcome measure

  • Cohort 1 Part 1: To determine the KRT-232 RP2D. [ 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 [ Time Frame: 10 Weeks ]
  • Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab [ Time Frame: 28 Days ]
  • Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC [ 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. [ 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. [ Time Frame: 10 Weeks ]

Central Contacts and Locations

Central contacts

John Mei

650-542-0136jmei@kartosthera.com

Emily Houlihan

401-954-8042ehoulihan@kartosthera.com

Locations

University of Colorado Anschutz Medical Campus

Recruiting

Aurora, Colorado, United States, 80045

Miami Cancer Institute

Recruiting

Miami, Florida, United States, 33176

Moffitt

Recruiting

Tampa, Florida, United States, 33612

Northwestern Memorial Hospital

Recruiting

Chicago, Illinois, United States, 60612

Norton Healthcare

Recruiting

Louisville, Kentucky, United States, 40202

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215-5418

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Memorial Sloan-Kettering Cancer Center

Recruiting

New York, New York, United States, 10021

Mount Sinai Hospital

Recruiting

New York, New York, United States, 10029

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

University of Texas MD Anderson

Recruiting

Houston, Texas, United States, 77030

Inova Health Care Services

Recruiting

Fairfax, Virginia, United States, 22031

Princess Margaret Cancer Centre

Recruiting

Toronto, Canada

More Information

Sponsor

Kartos Therapeutics, Inc.

Last update posted

Mar 2, 2023

Last verified

Feb, 2023

Keywords

  • navtemadlin (KRT-232)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Kartos Therapeutics, Inc. on 2023-03-02.