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

Trial ID or NCT#

NCT03068351

Status

recruiting iconRECRUITING

Purpose

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.

Official Title

Open-label, Multicenter, Dose-escalation/Expansion Phase Ib Study to Evaluate Safety, Pharmacokinetics, and Activity of BET Inhibitor RO6870810, Given as Mono- and Combination Therapy to Patients With Advanced Multiple Myeloma

Eligibility Criteria

Ages Eligible for Study: Older than 18 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Inclusion Criteria:
  1. - Performance status 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:
  1. - 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 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.

Investigator(s)

Michaela Liedtke
Michaela Liedtke
Hematologist-Oncologist
Associate Professor of Medicine (Hematology)
Rondeep Brar
Rondeep Brar
Hematologist-Oncologist
Clinical Associate Professor, Medicine - Hematology

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Contact

Jeffrey N. Sanders
6507244926