Status:
COMPLETED
A Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Participants With Relapsed and Refractory Multiple Myeloma
Lead Sponsor:
Hoffmann-La Roche
Conditions:
Multiple Myeloma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This open-label, randomized, multicenter, triple-arm Phase Ib/II study is designed to assess the efficacy, safety, tolerability, and pharmacokinetics of cobimetinib administered as a single agent (Arm...
Eligibility Criteria
Inclusion
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Life expectancy of at least 12 weeks
- Documented multiple myeloma
- Received 3 to 5 prior lines of therapy for multiple myeloma, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
- Achieved a response (minimal response \[MR\] or better) to at least one prior regimen
- Documented evidence of progressive disease (as defined by the IMWG criteria) on or after their last prior therapy, or participants who were intolerant to their last prior therapy
- Toxicities resulting from previous therapy (including peripheral neuropathy) that must be resolved or stabilized to Grade 1
Exclusion
- Anti-myeloma treatment within 14 days or 5 pharmacokinetic (PK) half-lives of the treatment, whichever is longer, before the date of randomization
- Completion of autologous stem cell transplant within 100 days prior to the date of randomization
- Prior allogeneic stem cell transplant as well as prior solid organ transplant
- Spinal cord compression not definitively treated with surgery and/or radiation
- Prior treatment with MEK inhibitors, B-cell lymphoma-2 (Bcl-2) inhibitors, or immune checkpoint inhibitor therapies including anti-cytotoxic T-lymphocyte associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1)
- Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication within 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
- Prior radiation therapy within 14 days prior to study enrollment and/or persistence of radiation-related adverse effects
- History or evidence of retinal pathology on ophthalmic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
- Left ventricular ejection fraction (LVEF) below institutional lower limit of normal
- History of clinically significant cardiovascular dysfunction
- Any previous venous thromboembolism greater than (\>) Grade 3 within 12 months of study enrollment
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins (for participants in Arm C only)
- History of other malignancy that could affect compliance with the protocol or interpretation of results
- Active or history of autoimmune disease or immune deficiency
- History of malabsorption or other condition that would interfere with absorption of study drugs
- Active tuberculosis
- Severe infection within 28 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment
- Positive test results for hepatitis B (hepatitis B surface antigen \[HBsAg\] and/or total hepatitis B core antibody \[HBcAb\]) or hepatitis C virus (HCV) antibody
- Known history of human immunodeficiency virus (HIV) seropositivity
- Treatment with a live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior to Cycle 1 Day 1, at any time during the study, and for at least 5 months after the last dose of study drug (for participants in Arm C only)
- Received strong cytochrome P-3A (CYP3A) inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, and moderate CYP3A inducers within 7 days prior to the initiation of study treatment
Key Trial Info
Start Date :
November 13 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 18 2021
Estimated Enrollment :
49 Patients enrolled
Trial Details
Trial ID
NCT03312530
Start Date
November 13 2017
End Date
May 18 2021
Last Update
February 28 2023
Active Locations (26)
Enter a location and click search to find clinical trials sorted by distance.
1
Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika
Brno, Czechia, 625 00
2
Fakultni nemocnice Ostrava; Klinika hematoonkologie
Ostrava, Czechia, 708 52
3
Univerzita Karlova v Praze a Vseobecna fakultni nemocnice v Praze - 1; Lekarska Fakulta - I
Prague, Czechia, 128 08
4
Rigshospitalet; Hæmatologisk Klinik
København Ø, Denmark, 2100