Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma
Merkel Cell Carcinoma
About this trial
This is an interventional treatment trial for Merkel Cell Carcinoma focused on measuring navtemadlin (KRT-232)
Eligibility Criteria
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)
Sites / Locations
- University of Colorado Anschutz Medical CampusRecruiting
- Miami Cancer InstituteRecruiting
- MoffittRecruiting
- Northwestern Memorial HospitalRecruiting
- Norton HealthcareRecruiting
- Massachusetts General HospitalRecruiting
- Dana-Farber Cancer InstituteRecruiting
- University of MichiganRecruiting
- Memorial Sloan-Kettering Cancer CenterRecruiting
- Mount Sinai HospitalRecruiting
- Fox Chase Cancer Center
- UPMC Hillman Cancer CenterRecruiting
- University of Texas MD AndersonRecruiting
- Inova Health Care ServicesRecruiting
- Princess Alexandra Hospital OncologyRecruiting
- Centro Catarinense de Pesquisa (CECAP) - Hospital Santa Catarina de BlumenauRecruiting
- Instituto Nacional do CancerRecruiting
- Centro Intergado de OncologiaRecruiting
- Centro de Pesquisa Clinica em OncologiaRecruiting
- Clinica De Neoplasias LitoralRecruiting
- Hospital PaulistanoRecruiting
- Princess Margaret Cancer CentreRecruiting
- CHU de Bordeaux- Hopital Saint-AndreRecruiting
- AP-HP Universite Paris SaclayRecruiting
- CHU de LilleRecruiting
- CHU Lyon-SudRecruiting
- Hôpital de la Timone. Aix-Marseille UniversitéRecruiting
- CHU MontpellierRecruiting
- CHU de NantesRecruiting
- Hôpital Saint Louis - APHPRecruiting
- CHU de ToursRecruiting
- Vivantes Network for Health Gmb, Neukölln ClinicRecruiting
- Universitätsklinikum ErlangenRecruiting
- Universitätsklinikum Essen (AöR)Recruiting
- Nationales Centrum für Tumorerkrankungen NCTRecruiting
- Uniklinik KolnRecruiting
- Universitätsklinik RostockRecruiting
- Universitats-Hautklinik TubingenRecruiting
- Institute for Cancer Research and TreatmentRecruiting
- Istituto Nazionale Tumori IRCCS Fondazione PascaleRecruiting
- AUSL della RomagnaRecruiting
- AOUS Le ScotteRecruiting
- OSP Civile Maggiore Borgo TrentoRecruiting
- National Cancer CenterRecruiting
- Seoul National University HospitalRecruiting
- Severance Hospital Yonsei University Health SystemRecruiting
- University Medical Center GroningenRecruiting
- Hospital Duran i ReynalsRecruiting
- Hospital General Universitario Gregorio Marañn (Madrid)Recruiting
- Complejo Hospitalario de NavarraRecruiting
- Fundacio Investigao Hospital General Universitario de ValenciaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Cohort 1, Arm 1
Cohort 1, Arm 1b
Cohort 1, Arm 2b
Cohort 1, Arm 3
Cohort 1, Arm 5
Cohort 1 Expansion
Cohort 2, Arm 1 KRT-232 in combination with avelumab
Cohort 2, Arm 2 KRT-232 in combination with avelumab
Cohort 2 Expansion
Cohort 3
Cohort 4
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.
KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
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.
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.
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.
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.