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 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.