solid tumors and Chronic Lymphocytic Leukemia
Conditions
Interventions
MSC2490484A is administered orally in a continuous dosing regimen over 21-day
cycles in the dose escalation and dose expansion cohorts. Patients can continue
on MSC2490484A until they withdraw conse
Sponsors
Merck
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: *Advanced solid tumors likely to have alterations in DNA repair mechanisms, such as the BRCA and ATM pathways), or CLL, with no other standard surgical, radiation, or systemic anticancer therapies available;*Tumor accessible for biopsies and agree to pretreatment tumor biopsy;*Measurable or evaluable disease in accordance with RECIST v 1.1 for solid tumors or Cheson*s criteria for CLL;*Male or female subjects at least 18 years of age who sign written informed consent.
Exclusion criteria
Exclusion criteria: 1. Eastern Cooperative Oncology Group performance status > 1;2. Received: a. Chemotherapy, immunotherapy, hormonal therapy with the exception of luteinizing hormone releasing hormone (LHRH) analogs, biologic therapy, or any other anticancer therapy within 28 days prior to the first dose of IMP administration (6 weeks for nitrosoureas or mitomycin C) b. Any investigational agent within 28 days prior to the first dose of IMP administration c. Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone marrow/stem cell transplantation within 5 years before study start. The extent of previous radiotherapy to the bone marrow will be determined by the investigator 3. Subjects currently receiving (or unable to stop using prior to receiving the first dose of trial drug) medications or herbal supplements known to be potent inhibitors of CYP3A or CYP2C19 (must stop at least 1 week prior), potent inducers of CYP3A or CYP2C19 (must stop at least 3 weeks prior), or drugs mainly metabolized by CYP3A with a narrow therapeutic index (must stop at least one day prior)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Dose Limiting Toxicities (DLTs) occurring in Cycle 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Pharmacokinetics profile in plasma (Cmax, tmax, Cmin, Cavg, fluctuation indices (peak-to-trough fluctuation and swing), AUC0-24, AUC0-12, AUC0-t, AUC0-*, AUC*, t1/2, *z, CL/f, Vz/f, Vss/f, Racc(AUC), and Racc(Cmax) 2)Best overall response rate 3) Clinical benefit rate defined as the proportion of subjects with Complete Response, Partial Response, or stable disease at Week 12 4) Progression-free survival time (PFS) | — |
Countries
Netherlands
Outcome results
None listed