study of bromodomain and extra-terminal protein (bet) inhibitor ro6870810 as mono- and combination therapy in advanced multiple myeloma

Conditions: Multiple Myeloma

Summary: 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.


Eligibility criteria:
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 (\ 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.