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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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/Phase 2
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
19/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2025
Actual
Sample size
Target
115
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
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03787602
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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03787602