Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma
Purpose
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.
Condition
- Merkel Cell Carcinoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts 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)
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
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. |
|
Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
More Details
- Status
- Recruiting
- Sponsor
- Kartos Therapeutics, Inc.