Merkel Cell Carcinoma
Conditions
Keywords
navtemadlin (KRT-232)
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.
Interventions
DRUGKRT-232
KRT-232 is an experimental MDM2 anticancer drug taken by mouth.
DRUGAvelumab
Avelumab is a PD-L1 blocking antibody anticancer drug administered by intravenous infusion.
Sponsors
Kartos Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 10 Weeks | ORR will be assessed per RECIST criteria 1.1 by IRC. |
| Cohort 1 Part 1: To determine the KRT-232 RP2D. | 10 Weeks | The Safety Review Committee (SRC) will determine RP2D for expansion based on safety and tolerability of each arm. |
| 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 | 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. |
| Cohort 2 Part 1: To determine the KRT-232 RP2D in combination with avelumab | 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. |
| Cohort 2 Part 2: To determine the objective response rate (ORR) in treatment-naïve subjects with p53WT MCC | 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. |
| 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. | 10 Weeks | ORR will be assessed per RECIST criteria 1.1 by IRC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To determine the duration of response (DoR) | 1 year after last subject enrolled | Time from documentation of response (CR or PR as determined by RECIST 1.1) until disease progression. |
| To determine Progression-free survival (PFS) | 1 year after last subject enrolled | Time from initial treatment until disease progression. |
| To determine overall survival (OS) | 1 year after last subject enrolled | Time from initial treatment until death from any cause. |
| To determine clinical benefit rate (CBR) | 1 year after last subject enrolled. | PR, CR or stable disease that last at least 10 weeks, per IRC or investigator assessment. |
| To determine the confirmed ORR based on investigator assessment. | 1 year after last subject enrolled. | ORR will be assessed per RECIST criteria 1.1 by investigators. |
Countries
Australia, Brazil, Canada, France, Germany, Italy, Netherlands, South Korea, Spain, United States
Contacts
Primary ContactJohn Mei
Backup ContactEmily Houlihan
Outcome results
None listed