A Phase 1b/2, Open-Label Study Evaluating the Safety and Efficacy of KRT-232 in Patients with p53 Wild-Type (p53WT)M erkel 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
- Merkel Cell Carcinoma (MCC)10040900
- Registration Number
- NL-OMON56137
- Lead Sponsor
- Kartos Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
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. Failure is defined as any
subject whose disease has progressed (by RECIST criteria) or those who are
intolerant to PD-1 inhibitor or PD-L1 inhibitor treatment. Any PD-1 inhibitor
or PD-L1 inhibitor may have been used at any time in the past, with no limit or
minimum duration required.
2. For Cohort 2, subjects must not have received any anti-PD-1 or
anti-PD-L1therapy.
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 (Eisenhauer 2009, Appendix 4).
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
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, organconfined 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
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Cohort 1 Part 1: Safety Review Committee (SRC) will determine recommended<br /><br>phase 2 dose (RP2D) for expansion based on safety and tolerability of each arm.<br /><br>- Cohort 1 Part 2: Objective Response Rate (ORR) as assessed per RECIST<br /><br>criteria version 1.1<br /><br>- Cohort 2 Part 1: Dose Limiting toxicity (DLT) will be used to establish the<br /><br>Maximum Tolerated Dose (MTD) of KRT-232 in combination with avelumab. SRC will<br /><br>determine the RP2D based on the safety of combination of KRT-232 with avelumab.<br /><br>- Cohort 2 Part 2: ORR will be assessed per RECIST criteria version 1.1<br /><br>- Cohort 3: ORR as assessed per RECIST criteria version 1.1 based on<br /><br>independent review committee (IRC) review of tumor assessments.<br /><br>- Cohort 4: ORR as assessed per RECIST criteria version 1.1 based on IRC review<br /><br>of tumor assessments.</p><br>
- Secondary Outcome Measures
Name Time Method