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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT03787602

Studienbeginn:
März 2019

Letztes Update:
02.03.2023

Wirkstoff:
KRT-232, Avelumab

Indikation (Clinical Trials):
Carcinoma, Merkel Cell, Carcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Kartos Therapeutics, Inc.

Collaborator:
-

Kontakt

Studienlocations
(3 von 51)

Vivantes Network for Health Gmb, Neukölln Clinic
Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Hautkrebszentrum Universitätsklinikum Erlangen
Ulmenweg 18
91054 Erlangen
(Bayern)
DeutschlandRekrutierend» Google-Maps
Universitätsklinikum Essen (AöR)
Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Nationales Centrum für Tumorerkrankungen NCT
Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Kopf-Hals-Tumor-Zentrum der Universitätsklinik Rostock
Doberaner Straße 137-139
18057 Rostock
DeutschlandRekrutierend» Google-Maps
Universitats-Hautklinik Tubingen
Tübingen
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
University of Colorado Anschutz Medical Campus
80045 Aurora
United StatesRekrutierend» Google-Maps
Northwestern Memorial Hospital
60612 Chicago
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps
Dana-Farber Cancer Institute
02215-5418 Boston
United StatesRekrutierend» Google-Maps
University of Michigan
48109 Ann Arbor
United StatesRekrutierend» Google-Maps
Memorial Sloan-Kettering Cancer Center
10021 New York
United StatesRekrutierend» Google-Maps
Fox Chase Cancer Center
19111-2434 Philadelphia
United StatesAktiv, nicht rekrutierend» Google-Maps
UPMC Hillman Cancer Center
15232 Pittsburgh
United StatesRekrutierend» Google-Maps
University of Texas MD Anderson
77030 Houston
United StatesRekrutierend» Google-Maps
Inova Health Care Services
22031 Fairfax
United StatesRekrutierend» Google-Maps
Princess Alexandra Hospital Oncology
Woolloongabba
AustraliaRekrutierend» Google-Maps
Centro Catarinense de Pesquisa (CECAP) - Hospital Santa Catarina de Blumenau
Blumenau
BrazilRekrutierend» Google-Maps
Centro de Pesquisa Clinica em Oncologia
Ijuí
BrazilRekrutierend» Google-Maps
CHU de Bordeaux- Hopital Saint-Andre
Bordeaux
FranceRekrutierend» Google-Maps
AP-HP Universite Paris Saclay
Gif-sur-Yvette
FranceRekrutierend» Google-Maps
Hôpital de la Timone. Aix-Marseille Université
Cedex 5 Marseille
FranceRekrutierend» Google-Maps
Institute for Cancer Research and Treatment
Candiolo
ItalyRekrutierend» Google-Maps
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Napoli
ItalyRekrutierend» Google-Maps
National Cancer Center
Goyang-si
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Severance Hospital Yonsei University Health System
Seoul
Korea, Republic ofRekrutierend» Google-Maps
University Medical Center Groningen
Groningen
NetherlandsRekrutierend» Google-Maps
Hospital General Universitario Gregorio Marañn (Madrid)
Madrid
SpainRekrutierend» Google-Maps
Fundacio Investigao Hospital General Universitario de Valencia
Valencia
SpainRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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)

Studien-Rationale

Primary outcome:

1. Cohort 1 Part 1: To determine the KRT-232 RP2D. (Time Frame - 10 Weeks):
The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm.

2. 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):
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.

3. Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab (Time Frame - 28 Days):
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.

4. Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC (Time Frame - 10 Weeks):
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.

5. 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):
ORR will be assessed per RECIST criteria 1.1 by IRC.

6. 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):
ORR will be assessed per RECIST criteria 1.1 by IRC.

Secondary outcome:

1. To determine the confirmed ORR based on investigator assessment. (Time Frame - 1 year after last subject enrolled.):
ORR will be assessed per RECIST criteria 1.1 by investigators.

2. To determine the duration of response (DoR) (Time Frame - 1 year after last subject enrolled):
Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression.

3. To determine Progression-free survival (PFS) (Time Frame - 1 year after last subject enrolled):
Time from initial treatment until disease progression.

4. To determine overall survival (OS) (Time Frame - 1 year after last subject enrolled):
Time from initial treatment until death from any cause.

5. To determine clinical benefit rate (CBR) (Time Frame - 1 year after last subject enrolled.):
PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment.

Studien-Arme

  • 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.

Geprüfte Regime

  • KRT-232 (navtemadlin):
    KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
  • Avelumab (Bavencio):
    Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.

Quelle: ClinicalTrials.gov


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