Navtemadlin (KRT-232) With or Without Anti-PD-1/Anti-PD-L1 for the Treatment of Patients With Merkel Cell Carcinoma
Status and phase
Enrolling
Phase 2
Phase 1
Conditions
Merkel Cell Carcinoma
Treatments
Drug: KRT-232
Drug: Avelumab
Details and patient eligibility
About
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.
Enrollment
115 estimated patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
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)
Trial design
Primary purpose
Treatment
Allocation
Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
115 participants in 11 patient groups
Cohort 1, Arm 1
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
Treatment:
Drug: KRT-232
Cohort 1, Arm 1b
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 23-day cycle.
Treatment:
Drug: KRT-232
Cohort 1, Arm 2b
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) on Days 1-5 in a 28-day cycle.
Treatment:
Drug: KRT-232
Cohort 1, Arm 3
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 21-day cycle.
Treatment:
Drug: KRT-232
Cohort 1, Arm 5
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) on Days 1-7 in a 28-day cycle.
Treatment:
Drug: KRT-232
Cohort 1 Expansion
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Treatment:
Drug: KRT-232
Cohort 2, Arm 1 KRT-232 in combination with avelumab
Experimental group
Description:
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.
Treatment:
Drug: Avelumab
Drug: KRT-232
Cohort 2, Arm 2 KRT-232 in combination with avelumab
Experimental group
Description:
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.
Treatment:
Drug: Avelumab
Drug: KRT-232
Cohort 2 Expansion
Experimental group
Description:
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.
Treatment:
Drug: Avelumab
Drug: KRT-232
Cohort 3
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Treatment:
Drug: KRT-232
Cohort 4
Experimental group
Description:
KRT-232 will be administered orally, once daily (QD) per Cohort 1 RP2D dose and schedule.
Treatment:
Drug: KRT-232
Trial contacts and locations
51
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Central trial contact
John Mei; Emily Houlihan
Data sourced from clinicaltrials.gov
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