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Sponsor: Hoffmann-La Roche
Conditions: Multiple Myeloma
Interventions: RO6870810, daratumumab
Countries: United States, Australia, United Kingdom
This is a Phase Ib, open-label, multicenter, global study designed to assess the safety and tolerability of RO6870810 as monotherapy and in combination with daratumumab in participants with relapsed/refractory multiple myeloma. Each treatment cycle will be 21 days in length. There are two parts to this study. A dose-escalation phase (Part I) will be used to evaluate the safety and tolerability and dose limiting toxicities, and to establish the maximum tolerated dose (MTR)/optimum biological dose (OBD) of RO6870810 when given as monotherapy or in combination with daratumumab. A dose-expansion phase (Part II) will further characterize the safety, tolerability and activity of RO6870810 as monotherapy or in combination with daratumumab at the defined expansion dose-levels.
Sex: ALL
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
Inclusion Criteria: * Performance status \</=2 on the Eastern Cooperative Oncology Group (ECOG) scale * Life expectancy \> 3 months * Relapsed or refractory multiple myeloma. Participants with primary refractory myeloma only allowed in dose-escalation phase of the study. * Prior treatment: Treated with at least three prior lines of multiple myeloma therapy including a proteasome inhibitor and an immuno modulatory agent or who are double refractory to a proteasome inhibitor and an immuno modulatory agent. Prior anti-CD38 antibody (e.g., daratumumab, isatuximab) treatment is acceptable only for participants receiving monotherapy treatment. * Prior treatment: Treated with two or more lines of prior therapy, with disease refractory to both a proteasome inhibitor and an immunomodulatory agent, and disease progression (as defined by International Myeloma Working Group (IMWG) criteria) following treatment with an anti-CD38 monoclonal antibody given as monotherapy or in combination therapy. The most recent treatment regimen must have contained an anti-CD38 monoclonal antibody. * Treatment with prior autologous transplant is permitted * Documented diagnosis of symptomatic multiple myeloma, as defined by the IMWG * Measurable disease defined as at least one of the following: serum M-protein \>/=1 grams/deciliter (g/dL), urine M-protein \>/= 200 milligrams/24 hours (mg/24h), serum free light chain (SFLC) assay: involved SFLCs \>/= 10 mg/dL (\>/= 100 mg/L) and an abnormal SFLC ratio (\<0.26 or \>1.65). * Female participants of childbearing potential must have a negative serum pregnancy test within the 7 days prior to the first study drug administration. * For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 2 months after the last dose of RO6870810 as monotherapy, or for at least 3 months after the last dose of daratumumab. * For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 4 months after the last dose of RO6870810 as monotherapy, or for at least 3 months after the last dose of daratumumab. Exclusion Criteria: * Plasma cell leukemia defined as peripheral plasma cell count \> 2000/cubic millimeter (mm\^3) * For expansion cohorts only: Primary refractory multiple myeloma defined as disease that is non-responsive in participants who have never achieved a minimal response or better with any therapy * History of other malignancy within 2 years prior to screening, except for ductal carcinoma in situ not requiring chemotherapy, appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, low-grade, localized prostate cancer (Gleason score \</= 7) not requiring treatment or appropriately treated Stage I uterine cancer * POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) * Current or prior disease or treatment that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor * Pregnant or breastfeeding female. * Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the first dose of study treatment and during the study. * Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the first dose of study treatment and during the study. * Surgery within 21 days prior to study entry. * Prior treatment with small molecule BET family inhibitor or receiving steroids \>the equivalent of 10mg prednisone daily * participants who are currently receiving any other investigational agent or have received an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to study entry * Uncontrolled cancer pain * Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 14 days except for alkylating agents (e.g., melphalan) within 28 days.
- Duarte, California, United States
- Stanford, California, United States
- Jacksonville, Florida, United States
- Atlanta, Georgia, United States
- Boston, Massachusetts, United States
- New York, New York, United States
- Chapel Hill, North Carolina, United States
- Durham, North Carolina, United States
- Randwick, New South Wales, Australia
- Fitzroy, Victoria, Australia
- London, United Kingdom
- Oxford, United Kingdom