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

Phase 1

Conditions: p53 Wild-Type (p53WT) Merkel Cell Carcinoma (MCC)
MedDRA version: 21.1Level: LLTClassification code 10064025Term: Merkel cell carcinomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-002820-35-ES

Lead Sponsor: Kartos Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 104

Inclusion Criteria

1. For Cohort 1, 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. Adults = 18 years of age
4. ECOG performance status of 0 to 1
5. Histologically confirmed MCC. Disease must be measurable, with at least 1 measurable lesion by RECIST criteria, version 1.1
6. MCC expressing p53WT based on any CLIA or FDA approved test
7. Fresh or archival tumor tissue must be submitted for biomarker assessment. Archival tissue samples must have been obtained from biopsy performed = 2 years before the date of signing the informed consent for this study
8. 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
9. 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 52
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion Criteria

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)

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

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