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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03787602




Registration number
NCT03787602
Ethics application status
Date submitted
6/12/2018
Date registered
26/12/2018
Date last updated
2/03/2023

Titles & IDs
Public title
Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma
Scientific title
A Phase 1b/2, Open-Label Study Evaluating the Safety and Efficacy of KRT-232 in Patients With p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC) Who Have Failed 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
Secondary ID [1] 0 0
KRT-232-103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Merkel Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KRT-232
Treatment: Drugs - Avelumab

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.


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

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohort 1 Part 1: To determine the KRT-232 RP2D.
Timepoint [1] 0 0
10 Weeks
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
10 Weeks
Primary outcome [3] 0 0
Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab
Timepoint [3] 0 0
28 Days
Primary outcome [4] 0 0
Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC
Timepoint [4] 0 0
10 Weeks
Primary outcome [5] 0 0
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.
Timepoint [5] 0 0
10 Weeks
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
10 Weeks
Secondary outcome [1] 0 0
To determine the confirmed ORR based on investigator assessment.
Timepoint [1] 0 0
1 year after last subject enrolled.
Secondary outcome [2] 0 0
To determine the duration of response (DoR)
Timepoint [2] 0 0
1 year after last subject enrolled
Secondary outcome [3] 0 0
To determine Progression-free survival (PFS)
Timepoint [3] 0 0
1 year after last subject enrolled
Secondary outcome [4] 0 0
To determine overall survival (OS)
Timepoint [4] 0 0
1 year after last subject enrolled
Secondary outcome [5] 0 0
To determine clinical benefit rate (CBR)
Timepoint [5] 0 0
1 year after last subject enrolled.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Princess Alexandra Hospital Oncology - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Brazil
State/province [11] 0 0
Blumenau
Country [12] 0 0
Brazil
State/province [12] 0 0
Brasília
Country [13] 0 0
Brazil
State/province [13] 0 0
Curitiba
Country [14] 0 0
Brazil
State/province [14] 0 0
Ijuí
Country [15] 0 0
Brazil
State/province [15] 0 0
Itajai
Country [16] 0 0
Brazil
State/province [16] 0 0
São Paulo
Country [17] 0 0
Canada
State/province [17] 0 0
Toronto
Country [18] 0 0
France
State/province [18] 0 0
Bordeaux
Country [19] 0 0
France
State/province [19] 0 0
Gif-sur-Yvette
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Montpellier
Country [24] 0 0
France
State/province [24] 0 0
Nantes
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
France
State/province [26] 0 0
Tours
Country [27] 0 0
Germany
State/province [27] 0 0
Berlin
Country [28] 0 0
Germany
State/province [28] 0 0
Erlangen
Country [29] 0 0
Germany
State/province [29] 0 0
Essen
Country [30] 0 0
Germany
State/province [30] 0 0
Heidelberg
Country [31] 0 0
Germany
State/province [31] 0 0
Köln
Country [32] 0 0
Germany
State/province [32] 0 0
Rostock
Country [33] 0 0
Germany
State/province [33] 0 0
Tübingen
Country [34] 0 0
Italy
State/province [34] 0 0
Candiolo
Country [35] 0 0
Italy
State/province [35] 0 0
Napoli
Country [36] 0 0
Italy
State/province [36] 0 0
Ravenna
Country [37] 0 0
Italy
State/province [37] 0 0
Siena
Country [38] 0 0
Italy
State/province [38] 0 0
Verona
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Goyang-si
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Seoul
Country [41] 0 0
Netherlands
State/province [41] 0 0
Groningen
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid
Country [44] 0 0
Spain
State/province [44] 0 0
Pamplona
Country [45] 0 0
Spain
State/province [45] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kartos Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
John Mei
Address 0 0
Country 0 0
Phone 0 0
650-542-0136
Fax 0 0
Email 0 0
jmei@kartosthera.com
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.