M3541 in Combination With Radiotherapy in Subjects With Solid Tumors

• Status: Completed
• Trial end date: 2020-04-27
• Target enrollment: 0
• Participant gender: All

Summary

This dose-escalation study will evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and explore antitumor activity of M3541 in combination with fractionated palliative radiotherapy (RT) in subjects with solid tumors with malignant lesions in the thorax, abdominal cavity, head and neck region, or extremities likely to benefit from palliative RT.

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

Details

• Lead Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA; Merck KGaA, Darmstadt, Germany

Criteria

Inclusion Criteria:

• Subjects must have solid tumors with malignant lesions in the thorax, abdominal cavity, head and neck region, or extremities (any histology) likely to benefit from palliative radiotherapy; subjects requiring palliative RT for lesions in the spine or lesions adjacent to the spinal cord are excluded from this study

• Eastern Cooperative Oncology Group performance status (ECOG PS) =< 2

• Life expectancy >= 3 months

• Adequate hematologic, hepatic, and renal function

• Agree to use highly effective contraception (that is, methods with a failure rate of less than 1 percent per year) if the subject is male or a female of childbearing potential (female partners of childbearing potential of male subjects must also agree to use highly effective contraception)

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Use of other anticancer therapy within 15 days before the first dose of M3541 administration and should not be within the "at risk follow-up period" for that specific anticancer therapy. The use of any investigational agent is not allowed within 28 days before the first dose of M3541

• Residual toxicity due to previous anticancer therapy with no return to baseline or =< Grade 1 (except alopecia) according to CTCAE V4.03

• Extensive prior RT on more than 30 percent of bone marrow reserves (by Investigator judgment), or prior bone marrow/stem cell transplantation within 5 years before study start

• Prior RT to the same region that would be irradiated in this study

• Subjects at increased risk for radiation toxicities, such as known collagen vascular disease (example, scleroderma, Sjogren's disease, etc) or other inherited radiation hypersensitivity syndromes (example, Gorlin syndrome, Fanconi anemia, ataxia-telangiectasia, etc.)

• Surgical intervention within 28 days prior to the first dose of M3541 administration

• Known central nervous system metastases causing clinical symptoms or metastases that require therapeutic intervention. Subjects with a history of treated central nervous system (CNS) metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy. Subjects with CNS metastases incidentally detected during Screening that do not cause clinical symptoms and for which standard of care suggests no therapeutic intervention is indicated, should be discussed with the Sponsor Medical Responsible

• Active difficulty swallowing, malabsorption or other chronic gastrointestinal disease or conditions (including pancreas deficiency requiring Creon therapy) that may hamper compliance and/or absorption of M3541

• Subjects currently receiving or unable to stop using medications or herbal supplements known to be potent inhibitors of cytochrome P450 (CYP) 3A and / or P-glycoprotein (P-gp) (CYP and / P-gp must stop at least 1 week before treatment with M3541) or potent inducers of CYP3A or P-gp (must stop at least 3 weeks before treatment with M3541) or drugs mainly metabolized by CYP3A with a narrow therapeutic index (must stop at least 1 day prior).

• Other protocol defined exclusion criteria could apply