Clinical Phase I Study Investigating MSC2490484A, an Inhibitor of a DNA-dependent Protein Kinase, in Advanced Solid Tumors or Chronic Lymphocytic Leukemia

• Status: Completed
• Trial end date: 2017-06-29
• Target enrollment: 0
• Participant gender: All

Summary

MSC2490484A is an investigational drug that is being evaluated for the treatment of subjects with advanced solid tumors or chronic lymphocytic leukemia (CLL) that likely differs from other cancers in how it repairs damaged DNA (genetic material). This is a first-in-man Phase I study, which means that it is the first time the study drug is being used in humans. The main purpose is to determine the highest dose that does not cause unacceptable side effects. The second is to determine the appropriate dose to use in future research for subjects with cancer. Othergoals of the study are to learn about the drug's safety and side effects, how it affects the tumor, and how the body processes the drug.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Treatments: Peposertib

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. Subjects with CLL will be enrolled in 1 of the RP2D expansion cohorts only

• 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.

• Other protocol-defined criteria could apply

Exclusion Criteria:

• Eastern Cooperative Oncology Group performance status > 1

• Prior treatment with chemotherapy, immunotherapy, hormonal therapy, with the exception of luteinizing hormone releasing hormone (LHRH) analogs, biologic therapy, any other anticancer therapy, or any other investigational agent within 28 days of the first dose of MSC2490484A (6 weeks for nitrosoureas or mitomycin C)

• Extensive prior radiotherapy on more than 30% of bone marrow reserves or prior bone marrow/stem cell transplantation within 5 years of study start. The extent of previous radiotherapy to the bone marrow will be determined by the investigator.

• Receiving medications or herbal supplements that are known to be potent inhibitors of cytochrome P450 3A4 or inducers of cytochrome P450 3A4.

• Not recovered from toxicity due to prior therapy to baseline or an AE CTCAE Grade of 1 or less (except alopecia)

• Poor vital organ function as defined in the protocol

• Significant cardiac conduction abnormalities as defined in the protocol

• Central nervous system metastases unless previously radiotherapy treated, stable by computerized tomography (CT) scan for at least 3 months without evidence of cerebral edema, and no requirements for corticosteroids or anticonvulsants

• Other protocol-defined criteria could apply