Study of Bromodomain and Extra-Terminal Protein (BET) Inhibitor RO6870810 as Mono- and Combination Therapy in Advanced Multiple Myeloma

Inclusion Criteria:

Performance status 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 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.