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
- Conditions
- p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC)MedDRA version: 21.1Level: LLTClassification code 10064025Term: Merkel cell carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002820-35-DE
- Lead Sponsor
- Kartos Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 175
1.For Cohorts 1, 3 and 4, subjects must have failed treatment with at least one PD-1 inhibitor or PD-L1 inhibitor for metastatic MCC
2.For Cohort 2, subjects must not have received any anti-PD-1 or anti-PD-L1 treatments for metastatic MCC
3.For Cohort 3, subjects must not have received any prior chemotherapy.
4.For Cohort 4, subjects must have received at least 1 line of prior chemotherapy
5.Adults = 18 years of age and willing to provide written informed consent
6.ECOG performance status of 0 to 1
7.Histologically confirmed MCC. Disease must be measurable, with at least 1 measurable lesion by RECIST criteria, version 1.1
8.For Cohorts 1 and 2: MCC expressing p53WT based on any CLIA or FDA approved sequencing test or by a test approved by the local health authority or, if not available, by a validated test. For Cohort 2, subjects may be enrolled and treated with avelumab monotherapy before p53WT status is known
9.For Cohorts 3 and 4: MCC expressing p53WT based on Central Laboratory testing
10.Fresh or archival tumor tissue must be submitted for biomarker assessment.
11.Adequate hematological, hepatic, and renal function within 14 days prior to the first dose of KRT-232 as defined in more detail in the protocol
12.Agree to comply with contraception requirements as defined in more detail in the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 87
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 88
1. 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
2. Concurrent anticancer treatment such as chemotherapy, cytoreductive therapy, immune therapy, or cytokine therapy within 28 days or approximately 5 half-lives, whichever is shorter, prior to the first dose of KRT-232
3. Radiation therapy within 2 weeks prior to the first dose of KRT-232
4. Toxicity from prior radiation therapy that has not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 0 or Grade 1 (with the exception of Grade 2 alopecia)
5. Participation in another interventional clinical trial within the past 4 weeks of the first dose of KRT 232 (participation in observational studies is permitted)
6. Patients previously treated with MDM2 antagonist therapies or p53-directed therapies
7. Women who are pregnant or breastfeeding
8. History of major organ transplant
9. Subjects with known central nervous system (CNS) metastases that are previously untreated
10. Uncontrolled intercurrent illness including, but not limited to, acute hepatitis A; known history of human immunodeficiency virus (HIV)-positive; clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure; unstable angina pectoris; ventricular arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements
11. Subjects with clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy. Subjects with acute bacterial infections requiring antibiotic use should delay screening/ enrollment until the course of antibiotic therapy has been completed.
12. Other malignancy within the last 3 years, other than chronic lymphocytic leukemia (CLL), curatively
treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or
treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma. Patients with CLL must not in the opinion of the investigator require or be receiving any treatment for their CLL in order to be eligible.
13. Grade 2 or higher QTc prolongation (>480 milliseconds per NCI-CTCAE criteria, version 5.0)
14. Known hypersensitivity or contraindications to any of the study drugs, required prophylaxes or their excipients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method